MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Trends in Cell Biology' source. Wed, 17 Mar 2010 17:03:48 +0100 http://www.medworm.com/index.php?rid=3347405&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20207148%26dopt%3DAbstract Authors: Ayers KL, Thérond PP The Hedgehog signalling pathway controls numerous developmental processes. In response to Hedgehog, Smoothened (Smo), a seven-pass transmembrane protein, orchestrates pathway signalling and controls transcription factor activation. In the absence of Hedgehog, the receptor Patched indirectly inhibits Smo in a catalytic manner. Many questions surrounding Smo activation and signalling remain. Recent findings in Drosophila and vertebrate systems have provided strong evidence that Smo acts as a G-protein-coupled receptor. We discuss the role and regulation of Smo and reassess similarities between Smo and G-protein-coupled receptors. We also examine recently identified members of the invertebrate and vertebrate Smo signalling cascades that are typical compo... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3347405 Thu, 04 Mar 2010 00:00:00 +0100 3347405 http://www.medworm.com/index.php?rid=3322789&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20189809%26dopt%3DAbstract Authors: Miura K, Hasegawa PM Post-translational modifications diversify proteome activity to mediate complex hierarchical regulatory processes that are crucial to eukaryotic cell function. Protein modification by Ub (ubiquitin) and Ubls (ubiquitin-like proteins) in plants, as in yeast and metazoans, is necessary for numerous cellular and developmental processes and for the genetic reprogramming that occurs in response to hormonal stimuli, host-pathogen interaction-related stimuli and environmental stimuli. Ub and Ubl modifications, such as sumoylation, facilitate molecular interaction with specific substrates. Recent evidence has permitted inference of the mechanisms by which Ubl modifications regulate physiological processes such as cell-cycle progression, abscisic acid signaling, de... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3322789 Fri, 26 Feb 2010 00:00:00 +0100 3322789 http://www.medworm.com/index.php?rid=3322790&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20188563%26dopt%3DAbstract Authors: Walsh DW, Godson C, Brazil DP, Martin F Developmental processes are regulated by the bone morphogenetic protein (BMP) family of secreted molecules. BMPs bind to serine/threonine kinase receptors and signal through the canonical Smad pathway and other intracellular effectors. Integral to the control of BMPs is a diverse group of secreted BMP antagonists that bind to BMPs and prevent engagement with their cognate receptors. Tight temporospatial regulation of both BMP and BMP-antagonist expression provides an exquisite control system for developing tissues. Additional facets of BMP-antagonist biology, such as crosstalk with Wnt and Sonic hedgehog signaling during development, have been revealed in recent years. In addition, previously unappreciated roles for the BMP antagonists i... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3322790 Wed, 24 Feb 2010 00:00:00 +0100 3322790 http://www.medworm.com/index.php?rid=3312297&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20172729%26dopt%3DAbstract Authors: Wade M, Wang YV, Wahl GM The activities of p53 cover diverse aspects of cell biology, including cell cycle control, apoptosis, metabolism, fertility, differentiation and cellular reprogramming. Although loss of p53 function engenders tumor susceptibility, hyperactivation of p53 is lethal. Therefore, p53 activity must be strictly regulated to maintain normal tissue homeostasis. Critical for the control of p53 function are its two main negative regulators: Mdm2 and Mdmx. Recent reports have provided insight into the complex mechanisms that regulate these two proteins and have revealed novel functions for each. Here, we review and evaluate models of Mdm2- and Mdmx-dependent regulation of p53 activity. Both Mdm2 and Mdmx receive input from numerous signaling pathways and interact ... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3312297 Fri, 19 Feb 2010 00:00:00 +0100 3312297 http://www.medworm.com/index.php?rid=3286611&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20153966%26dopt%3DAbstract Authors: Salomoni P, Calegari F The potential to increase unlimitedly in number and to generate differentiated cell types is a key feature of somatic stem cells. Within the nervous system, cellular and environmental determinants tightly control the expansion and differentiation of neural stem cells. Importantly, a number of studies have indicated that changes in cell cycle length can influence development and physiopathology of the nervous system, and might have played a role during evolution of the mammalian brain. Specifically, it has been suggested that the length of G1 can directly influence the differentiation of neural precursors. This has prompted the proposal of a model to explain how manipulation of G1 length can be used to expand neural stem cells. If validated in non-neural ... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3286611 Fri, 12 Feb 2010 00:00:00 +0100 3286611 http://www.medworm.com/index.php?rid=3286612&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20153650%26dopt%3DAbstract Authors: Hansen CG, Nichols BJ Caveolae are ampullate (flask-shaped) invaginations that are abundant in the plasma membrane of many mammalian cell types. Although caveolae are implicated in a wide range of processes including endothelial transcytosis, lipid homeostasis and cellular signalling, a detailed molecular picture of many aspects of their function has been elusive. Until recently, the only extensively characterised protein components of caveolae were the caveolins. Recently, data from several laboratories have demonstrated that a family of four related proteins, termed cavins 1-4, plays key roles in caveolar biogenesis and function. Salient properties of the cavin family include their propensity to form complexes with each other and their different but overlapping tissue distri... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3286612 Thu, 11 Feb 2010 00:00:00 +0100 3286612 http://www.medworm.com/index.php?rid=3255448&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20138522%26dopt%3DAbstract Authors: Lauwers E, Erpapazoglou Z, Haguenauer-Tsapis R, André B Yeast permeases, that act as transporters for nutrients including amino acids, nucleobases and metals, provide a powerful model system for dissecting the physiological control of membrane protein trafficking. Modification of these transporters by ubiquitin is known to target them for degradation in the vacuole, the degradation organelle of fungi. Recent studies have uncovered the role of specific adaptors for recruiting the Rsp5 ubiquitin ligase to these proteins. In addition, the role of ubiquitin at different trafficking steps including early endocytosis, sorting into the multivesicular body (MVB) pathway and Golgi-to-endosome transit is now becoming clear. In particular, K63-linked ubiquitin chains now emerge as a... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3255448 Thu, 04 Feb 2010 00:00:00 +0100 3255448 http://www.medworm.com/index.php?rid=3255449&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20137953%26dopt%3DAbstract Authors: Radulescu AE, Cleveland DW The large nuclear mitotic apparatus (NuMA) protein is an abundant component of interphase nuclei and an essential player in mitotic spindle assembly and maintenance. With its partner, cytoplasmic dynein, NuMA uses its cross-linking properties to tether microtubules to spindle poles. NuMA and its invertebrate homologs play a similar tethering role at the cell cortex, thereby mediating essential asymmetric divisions during development. Despite its maintenance as a nuclear component for decades after the final mitosis of many cell types (including neurons), an interphase role for NuMA remains to be established, although its structural properties implicate it as a component of a nuclear scaffold, perhaps as a central constituent of the proposed nuclear m... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3255449 Wed, 03 Feb 2010 00:00:00 +0100 3255449 http://www.medworm.com/index.php?rid=3245166&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20133134%26dopt%3DAbstract Authors: Bernstein BW, Bamburg JR Recent findings have significantly expanded our understanding of the regulation of actin-depolymerizing factor (ADF)/cofilin proteins and the profound multifaceted impact that these well-established regulators of actin dynamics have on cell biology. In this review we discuss new aspects of previously documented regulation, such as phosphorylation, but also cover novel recently established modes of regulation and functions of ADF (also known as destrin)/cofilin. We now understand that their activity responds to a vast array of inputs far greater than previously appreciated and that these proteins not only feed back to the crucially important dynamics of actin, but also to apoptosis cascades, phospholipid metabolism, and gene expression. We argue that th... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3245166 Tue, 02 Feb 2010 00:00:00 +0100 3245166 http://www.medworm.com/index.php?rid=3245167&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20129784%26dopt%3DAbstract Authors: Collins CA, Brown EJ Ubiquitin was first described as a tag allowing cells to degrade and recycle their own proteins. Recent research has shown ubiquitin to be central for immune system recognition of invading bacteria. This review describes a set of complex host-pathogen interactions that are dependent on ubiquitination. From the host perspective, ubiquitin-dependent activation of inflammation and degradation of bacterial effectors is protective. Several pathogens become ubiquitinated in the host cell cytosol, and recent research suggests that this could trigger a form of autophagy, increasingly recognized as an important mechanism for the control of infection by a variety of human pathogens. Meanwhile, bacteria have developed mechanisms to evade or exploit the fundamental pr... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3245167 Mon, 01 Feb 2010 00:00:00 +0100 3245167 http://www.medworm.com/index.php?rid=3189530&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20080406%26dopt%3DAbstract Authors: Wong JL, Johnson MA Eukaryotes employ a diversity of strategies to ensure that gametes come together, but the cellular climax is less varied: gamete plasma membranes must fuse to allow the combination of parental genomes. Recent studies of HAP2-GCS1, a sex-restricted transmembrane protein found in genomes representing all major eukaryotic taxa except fungi, suggest that a broad array of eukaryotic organisms could share a common mechanism for gamete fusion. Plant, protozoan, and algal gametes carrying loss-of-function mutations in HAP2-GCS1 fail to fuse with their complements. We propose that HAP2-GCS1 is a crucial component of an ancient mechanism that mediates the fusion of gamete plasma membranes and could have been a key early innovation in the evolution of sexual reproduct... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3189530 Fri, 15 Jan 2010 00:00:00 +0100 3189530 http://www.medworm.com/index.php?rid=3179292&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20071173%26dopt%3DAbstract Authors: Van den Broeke C, Radu M, Chernoff J, Favoreel HW p21-activated protein kinases (Paks) are cytosolic serine/threonine protein kinases that act as effectors for small (p21) GTPases of the Cdc42 and Rac families. It has long been established that Paks play a major role in a host of vital cellular functions such as proliferation, survival and motility, and abnormal Pak function is associated with a number of human diseases. Here, we discuss emerging evidence that these enzymes also play a major role in the entry, replication and spread of many important pathogenic human viruses, including HIV. Careful assessment of the potential role of Paks in antiviral immunity will be pivotal to evaluate thoroughly the potential of agents that inhibit Pak as a new class of anti-viral therapeut... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3179292 Mon, 11 Jan 2010 00:00:00 +0100 3179292 http://www.medworm.com/index.php?rid=3179291&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20071174%26dopt%3DAbstract In this report, we suggest that these qualities allow prions to act as 'bet-hedging' devices that facilitate the adaptation of yeasts to stressful environments, and might speed the evolution of new traits. PMID: 20071174 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3179291 Mon, 11 Jan 2010 00:00:00 +0100 3179291 http://www.medworm.com/index.php?rid=3164624&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20061149%26dopt%3DAbstract Authors: Vakifahmetoglu-Norberg H, Zhivotovsky B Caspase-2, the most conserved member of the caspase family, has long been recognized as an important protein in the regulation of apoptosis. However, due to a lack of phenotype in caspase-2 knock-out mice, its precise role has been questioned. Recently, several publications have described new mechanisms regulating caspase-2 activation, including its role within an activating complex named the PIDDosome, linking caspase-2 function to p53. Consistent with this, evidence is accumulating for potential roles of caspase-2 in non-apoptotic processes, including cell cycle regulation and DNA repair. In addition, a tumor-suppressor function has been suggested for caspase-2. Here we discuss how different PIDDosome complexes could be involved in mec... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3164624 Fri, 08 Jan 2010 00:00:00 +0100 3164624 http://www.medworm.com/index.php?rid=3164623&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20061150%26dopt%3DAbstract Authors: Fletcher SJ, Rappoport JZ Polarised vesicle trafficking has been suggested to regulate cell migration. Understanding how this takes place has been complicated by the use of disparate assays and cellular models. Although polarised trafficking does occur in cell motility it is not clear which pathways are involved. We propose a model for migrating cells where caveolar endocytosis occurs at the rear of the adherent surface, whereas clathrin-mediated endocytosis takes place in the middle-to-front region of the cell. We also suggest there is evidence to support polarised recycling of internalised cargo to the leading edge of migrating cells. Further research is required to confirm our hypothesis and a systematic evaluation of multiple pathways within individual systems and across d... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3164623 Fri, 08 Jan 2010 00:00:00 +0100 3164623 http://www.medworm.com/index.php?rid=3164622&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20061151%26dopt%3DAbstract Authors: Zhou AX, Hartwig JH, Akyürek LM Filamins are large actin-binding proteins that stabilize delicate three-dimensional actin filament networks and link them to cellular membranes where they integrate cell architectural and signaling functions important for cell locomotion. Filamins have been shown to bind to proteins with diverse functions and are implicated in human genetic diseases including malformations of the skeleton, brain, and heart. Mouse models of filamin deficiency have advanced our understanding of the important roles filamins play in embryonic development and disease progression. These studies provide clear evidence that cytoskeletal filamin proteins integrate cell signaling, transcription and organ development. This review focuses on the emerging roles of filam... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3164622 Fri, 08 Jan 2010 00:00:00 +0100 3164622 http://www.medworm.com/index.php?rid=3164621&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20061152%26dopt%3DAbstract Authors: Steed E, Balda MS, Matter K Tight junctions are intercellular adhesion complexes in vertebrates that are required for the formation of functional epithelial and endothelial barriers. Their morphological appearance and biochemical composition, that includes large multimeric protein complexes, have long fostered the belief that they are relatively rigid, non-dynamic structures. Recent observations now suggest that at least some junctional elements and proteins can be very dynamic, and that such dynamic properties are important for different tight junction functions ranging from the regulation of paracellular permeability to junction-associated signalling mechanisms that guide cell behaviour. Combining such dynamic properties with existing tight junction models will help us to ad... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3164621 Fri, 08 Jan 2010 00:00:00 +0100 3164621 http://www.medworm.com/index.php?rid=3164620&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20061153%26dopt%3DAbstract Authors: Zhao T, Xu Y As the guardian of the genome, the tumor suppressor p53 prevents the accumulation of genetic mutations by inducing cell cycle arrest, apoptosis or senescence of somatic cells after genotoxic and oncogenic stresses. Recent studies have identified the roles of p53 in suppressing pluripotency and cellular dedifferentiation. In this context, p53 suppresses the self-renewal of embryonic stem cells after DNA damage and blocks the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). If the inactivation of p53 pathway is a prerequisite for successful reprogramming, these findings raise concerns for the genomic stability and tumorigenecity of iPSCs and their derivatives. Elucidation of the roles of p53 as a barrier to pluripotency and cellular dediff... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3164620 Fri, 08 Jan 2010 00:00:00 +0100 3164620 http://www.medworm.com/index.php?rid=3143060&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20045331%26dopt%3DAbstract In this report, we review data that corroborate the view that IFs function as highly specialized cytoskeletal stress proteins that promote cellular organization and homeostasis. PMID: 20045331 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3143060 Wed, 30 Dec 2009 00:00:00 +0100 3143060 http://www.medworm.com/index.php?rid=3061765&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19959362%26dopt%3DAbstract Authors: Hosking CR PMID: 19959362 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3061765 Tue, 01 Dec 2009 00:00:00 +0100 3061765 http://www.medworm.com/index.php?rid=3042143&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19944606%26dopt%3DAbstract Authors: Laird DW In recent years our understanding of connexins has advanced from viewing them simply as proteins with a surprisingly short lifespan that form gap junction channels. Connexins are now known to be multifaceted proteins at the core of many multiprotein complexes that link to structural junctional complexes and cytoskeletal elements, and also to the cellular machinery that facilitates their transport, assembly, function and internalization. Collectively, these connexin-binding proteins can be termed the 'gap junction proteome'. The mechanistic understanding of the gap junction proteome with regards to the dynamic life cycle of connexins has grown further in importance in light of the large number of human diseases attributed to connexin gene mutations and regulatory chang... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3042143 Wed, 25 Nov 2009 00:00:00 +0100 3042143 http://www.medworm.com/index.php?rid=3034182&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19931459%26dopt%3DAbstract Authors: Caldieri G, Buccione R Recent years have witnessed growing interest in the biology of invadopodia, proteolytically active protrusions formed by invasive tumor cells when cultured on an extracellular matrix (ECM). Although substantial progress has been made towards defining their basic elements and features, the need remains to understand how these components are recruited and, ultimately, how ECM degradation is so precisely localized. According to recent evidence, invadopodia are raft-like membrane domains where cholesterol levels are tightly regulated, and active transport of protease-delivering carriers is required for their function. On this basis we hypothesize that the correct delivery of cargo to invadopodia is ensured by a polarized, cholesterol-dependent trafficking me... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3034182 Wed, 18 Nov 2009 00:00:00 +0100 3034182 http://www.medworm.com/index.php?rid=3015892&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19926479%26dopt%3DAbstract Authors: Reddy AB, O'Neill JS Circadian rhythms permeate mammalian biology. They are manifested in the temporal organisation of behavioural, physiological, cellular and neuronal processes. Whereas it has been shown recently that these approximately 24-hour cycles are intrinsic to the cell and persist in vitro, internal synchrony in mammals is largely governed by the hypothalamic suprachiasmatic nuclei that facilitate anticipation of, and adaptation to, the solar cycle. Our timekeeping mechanism is deeply embedded in cell function and is modelled as a network of transcriptional and/or post-translational feedback loops. Concurrent with this, we are beginning to understand how this ancient timekeeper interacts with myriad cell systems, including signal transduction cascades and the cell c... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=3015892 Mon, 16 Nov 2009 00:00:00 +0100 3015892 http://www.medworm.com/index.php?rid=2978248&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19896850%26dopt%3DAbstract Authors: Stuermer CA The proteins reggie-1 and reggie-2 were originally discovered in neurons during axon regeneration. Subsequently, they were independently identified as markers of lipid rafts in flotation assays and were hence named flotillins. Since then, reggie/flotillin proteins have been found to be evolutionarily conserved and are present in all vertebrate cells - yet their function has remained elusive and controversial. Recent results now show that reggie/flotillin proteins are indeed necessary for axon regeneration and growth: no axons form when reggies/flotillins are downregulated and signaling pathways controlling actin dynamics are perturbed. Their widespread expression and conservation, however, suggest that these proteins regulate basic cellular functions beyond regener... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2978248 Thu, 05 Nov 2009 00:00:00 +0100 2978248 http://www.medworm.com/index.php?rid=2969206&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19889541%26dopt%3DAbstract Authors: Kerppola TK Polycomb Group (PcG) proteins are transcription regulatory proteins that control the expression of a variety of genes from early embryogenesis through birth to adulthood. PcG proteins form several complexes that are thought to collaborate to repress gene transcription. Individual PcG proteins have unique characteristics, and mutations in genes encoding different PcG proteins cause distinct phenotypes. Histone modifications have important roles in some PcG protein functions, but they are not universally required. The mechanisms of gene-specific recruitment, transcription repression, and selective derepression of genes by vertebrate PcG proteins are incompletely understood. Future studies of this enigmatic group of developmental regulators are certain to produce unan... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2969206 Mon, 02 Nov 2009 00:00:00 +0100 2969206 http://www.medworm.com/index.php?rid=2955153&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19879762%26dopt%3DAbstract Authors: Speidel D Apoptosis induced by p53 is firmly established as a central mechanism of tumour suppression. In addition to its complex functions as a nuclear transcription factor, p53 can act in the cytosol and mitochondria to promote apoptosis through transcription-independent mechanisms. Recent studies have shown that physical and functional interactions of p53 with various members of the Bcl-2 family provide the basis for this alternative route of p53-mediated cell death. However, different models of how these interactions promote apoptosis have been proposed. This review focuses on the mechanisms, regulation and physiological roles of transcription-independent p53 activities and highlights recent findings suggesting that the utilisation of these activities provides a promising ... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2955153 Thu, 29 Oct 2009 00:00:00 +0100 2955153 http://www.medworm.com/index.php?rid=2928032&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19854056%26dopt%3DAbstract Authors: Koszul R, Kleckner N Dramatic chromosome motion is a characteristic of mid-prophase of meiosis that is observed across broadly divergent eukaryotic phyla. Although the specific mechanisms underlying chromosome motions vary among organisms studied to date, the outcome is similar in all cases: vigorous back-and-forth movement (as fast as approximately 1mum/sec for budding yeast), led by chromosome ends (or near-end regions), and directed by cytoskeletal components via direct association through the nuclear envelope. The exact role(s) of these movements remains unknown, although an idea gaining currency is that movement serves as a stringency factor, eliminating unwanted inter-chromosomal associations or entanglements that have arisen as part of the homolog pairing process and, p... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2928032 Thu, 22 Oct 2009 00:00:00 +0100 2928032 http://www.medworm.com/index.php?rid=2924747&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19850480%26dopt%3DAbstract Authors: Sesti F, Liu S, Cai SQ A wealth of evidence underscores the tight link between oxidative stress, neurodegeneration and aging. When the level of excess reactive oxygen species (ROS) increases in the cell, a phenomenon characteristic of aging, DNA is damaged, proteins are oxidized, lipids are degraded and more ROS are produced, all culminating in significant cell injury. Recently we showed that in the nematode, Caenorhabditis elegans, oxidation of K(+) channels by ROS is a major mechanism underlying the loss of neuronal function. The C. elegans results support an argument that K(+) channels controlling neuronal excitability and survival might provide a common, functionally important substrate for ROS in aging mammals. Here we discuss the implications that oxidation of K(+) chann... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2924747 Tue, 20 Oct 2009 00:00:00 +0100 2924747 http://www.medworm.com/index.php?rid=2920662&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19846310%26dopt%3DAbstract Authors: Barlow CA, Laishram RS, Anderson RA While the presence of phosphoinositides in the nuclei of eukaryotes and the identity of the enzymes responsible for their metabolism have been known for some time, their functions in the nucleus are only now emerging. This is illustrated by the recent identification of effectors for nuclear phosphoinositides. Like the cytosolic phosphoinositide signaling pathway, nuclear phosphatidylinositol 4,5-bisphosphate (PI4,5P(2)) is at the center of the pathway and acts both as a messenger and as a precursor for many additional messengers. Here, recent advances in the understanding of nuclear phosphoinositide signaling and its functions are reviewed with an emphasis on PI4,5P(2) and its role in gene expression. The compartmentalization of nuclear phos... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2920662 Sun, 18 Oct 2009 23:00:00 +0100 2920662 http://www.medworm.com/index.php?rid=2912935&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19836954%26dopt%3DAbstract Authors: Lippincott-Schwartz J, Patterson GH Photoactivatable fluorescent proteins (PA-FPs) are molecules that switch to a new fluorescent state in response to activation to generate a high level of contrast. Over the past eight years, several types of PA-FPs have been developed. The PA-FPs fluoresce green or red, or convert from green to red in response to activating light. Others reversibly switch between 'off' and 'on' in response to light. The optical "highlighting" capability of PA-FPs has led to the rise of novel imaging techniques providing important new biological insights. These range from in cellulo pulse-chase labeling for tracking subpopulations of cells, organelles or proteins under physiological settings, to super-resolution imaging of single molecules for determining int... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2912935 Wed, 14 Oct 2009 23:00:00 +0100 2912935 http://www.medworm.com/index.php?rid=2912934&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19836955%26dopt%3DAbstract Authors: Kirchhausen T Our understanding of the clathrin-dependent endocytic pathway owes much to new visualization techniques. Budding coated pits and clathrin-coated structures are transient molecular machines with distinctive morphological characteristics, and fluorescently labeled versions of a variety of marker proteins have given us a tantalizing glimpse of the dynamics of the system in living cells. Recent live-cell imaging studies have revealed unexpected modes of coat assembly, with distinct kinetics, distinct recruitment of associated proteins, distinct requirements for the participation of actin and its accessory proteins, and apparently distinct mechanisms of membrane deformation. A crucial issue is to connect the events detected by light microscopy with the structures and ... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2912934 Wed, 14 Oct 2009 23:00:00 +0100 2912934 http://www.medworm.com/index.php?rid=2902260&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19833516%26dopt%3DAbstract Authors: Yanagida M The fission yeast Schizosaccharomyces pombe is an excellent model for cellular quiescence that can be achieved experimentally with nutritional limitations. The target of rapamycin complex (TORC) is known to be important for the transition between proliferation and quiescence from yeast to humans, and the recently identified TORC components, Tti1 and Tel2, might control all of the cellular phosphoinositide 3-kinase-related kinases. New pilot studies using deletion mutants and temperature-sensitive mutants suggest that up to approximately 1000 genes are required for quiescence, and approximately 300 of these, called superhousekeeping genes, also participate in proliferation. These latest findings suggest that genes controlling quiescence are conserved from yeast to hu... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2902260 Mon, 12 Oct 2009 23:00:00 +0100 2902260 http://www.medworm.com/index.php?rid=2902259&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19833517%26dopt%3DAbstract Authors: Hosking CR, Schwartz JL PMID: 19833517 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2902259 Mon, 12 Oct 2009 23:00:00 +0100 2902259 http://www.medworm.com/index.php?rid=2902258&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19833518%26dopt%3DAbstract Authors: Swedlow JR, Eliceiri KW Significant technical advances in imaging, molecular biology and genomics have fueled a revolution in cell biology, in that the molecular and structural processes of the cell are now visualized and measured routinely. Driving much of this recent development has been the advent of computational tools for the acquisition, visualization, analysis and dissemination of these datasets. These tools collectively make up a new subfield of computational biology called bioimage informatics, which is facilitated by open source approaches. We discuss why open source tools for image informatics in cell biology are needed, some of the key general attributes of what make an open source imaging application successful, and point to opportunities for further operability t... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2902258 Mon, 12 Oct 2009 23:00:00 +0100 2902258 http://www.medworm.com/index.php?rid=2888768&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19819144%26dopt%3DAbstract Authors: Larson DR, Singer RH, Zenklusen D Analyzing the expression of single genes in single cells appears minimalistic in comparison to gene expression studies based on more global approaches. However, stimulated by advances in imaging technologies, single-cell studies have become an essential tool in understanding the rules that govern gene expression. This quantitative view of single-cell gene expression is based on counting mRNAs in single cells, monitoring transcription in real time, and visualizing single proteins. Parallel advances in mathematical models based on stochastic, discrete descriptions of biochemical processes have provided crucial insights into the underlying cellular mechanisms that control expression. The view that has emerged is rooted in a probabilistic understa... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2888768 Wed, 07 Oct 2009 23:00:00 +0100 2888768 http://www.medworm.com/index.php?rid=2888767&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19819145%26dopt%3DAbstract Authors: Nagy Z, Soutoglou E Faithful repair of DNA damage is essential for the maintenance of genome integrity. Recent advances in the local induction of DNA damage and in cell biological imaging techniques have extended our understanding of DNA repair gained from biochemical and genetic approaches; these advances now reveal that the assembly of DNA repair complexes at sites of DNA damage is spatially and temporally regulated. Visualization of the dynamics of double strand breaks in living cells has also provided valuable insights into how chromosomal translocations form. Here we outline the most commonly used tools to induce and visualize the DNA repair process and we discuss the advantages and disadvantages inherent to each method. PMID: 19819145 [PubMed - as supplied by publish... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2888767 Wed, 07 Oct 2009 23:00:00 +0100 2888767 http://www.medworm.com/index.php?rid=2888766&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19819146%26dopt%3DAbstract Authors: Provenzano PP, Eliceiri KW, Keely PJ Understanding tissue architecture and physical and chemical reciprocity between cells and their microenvironment provides vital insights into key events in cancer metastasis, such as cell migration through three-dimensional (3D) extracellular matrices. Yet, many mechanistic details associated with metastasis remain elusive due to the difficulty of studying cancer cells in relevant 3D microenvironments. Recently, optical imaging has facilitated the direct observation of single cells as they undertake fundamental steps in the metastatic processes. Optical imaging is also providing novel 'optical biomarkers' with diagnostic potential that are linked to cell-motility pathways associated with metastasis, and these can to help guide new approache... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2888766 Wed, 07 Oct 2009 23:00:00 +0100 2888766 http://www.medworm.com/index.php?rid=2888765&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19819147%26dopt%3DAbstract Authors: Snapp EL Fluorescent Proteins (FPs) have revolutionized cell biology. The value of labeling and visualizing proteins in living cells is evident from the thousands of publications since the cloning of Green Fluorescent Protein (GFP). Biologists have been flooded with a cornucopia of FPs; however, the FP toolbox has not necessarily been optimized for cell biologists. Common FP plasmids are suboptimal for the construction of proteins fused to FP. More problematic are commercial and investigator-constructed FP-fusion proteins that disrupt important cellular targeting information. Even when cell biologists correctly construct FP-fusion proteins, it is rarely self-evident which FP should be used. Important FP information, such as oligomer formation or photostability, is often obscur... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2888765 Wed, 07 Oct 2009 23:00:00 +0100 2888765 http://www.medworm.com/index.php?rid=2888772&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19818623%26dopt%3DAbstract Authors: Balla T When cells are exposed to hormones that act on cell surface receptors, information is processed through the plasma membrane into the cell interior via second messengers generated in the inner leaflet of the plasma membrane. Individual biochemical steps along this cascade have been characterized from ligand binding to receptors through to activation of guanine nucleotide binding proteins and their downstream effectors such as adenylate cyclase or phospholipase C. However, the complexity of temporal and spatial integration of these molecular events requires that they are studied in intact cells. The great expansion of fluorescent techniques and improved imaging technologies such as confocal and TIRF microscopy combined with genetically-engineered protein modules has prov... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2888772 Tue, 06 Oct 2009 23:00:00 +0100 2888772 http://www.medworm.com/index.php?rid=2888771&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19818624%26dopt%3DAbstract Authors: Simon SM Microscopy, especially fluorescence microscopy, has proven to be a powerful method for studying biological processes. Unfortunately, some of the same features that make biological membranes powerful (for example, all of the action taking place across a narrow 4nm film) also make it difficult to visualize by fluorescence. Over the past 30 years, numerous tricks have been developed to narrow the plane over which data is collected. One approach, total internal reflection (TIR) fluorescence microscopy, is particularly well suited for studying membrane events. A key issue to address when using TIR to tackle a new biological problem is: how can one judge whether the signals being observed are actually the biological phenomena that one wishes to study? PMID: 19818624 [Pu... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2888771 Tue, 06 Oct 2009 23:00:00 +0100 2888771 http://www.medworm.com/index.php?rid=2888770&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19818625%26dopt%3DAbstract Authors: McDermott G, Le Gros MA, Knoechel CG, Uchida M, Larabell CA Soft X-ray tomography (SXT) is ideally suited to imaging sub-cellular architecture and organization, particularly in eukaryotic cells. SXT is similar in concept to the well-established medical diagnostic technique computed axial tomography (CAT), except SXT is capable of imaging with a spatial resolution of 50nm, or better. In SXT, cells are imaged using photons from a region of the spectrum known as the 'water window'. This results in quantitative, high-contrast images of intact, fully hydrated cells without the need to use contrast-enhancing agents. The cells that are visualized are in close-to-native, fully functional state. The utility of SXT has recently been enhanced by the development of high numerical aperture... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2888770 Tue, 06 Oct 2009 23:00:00 +0100 2888770 http://www.medworm.com/index.php?rid=2888769&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19818626%26dopt%3DAbstract Authors: Yakir-Tamang L, Gerst JE Cell polarity is necessary for cell division, morphogenesis and motility in eukaryotes, and is determined by dynamic control of the cytoskeleton and secretory pathway to promote directional growth. In yeast, three essential and tightly-regulated processes orchestrate polarization and facilitate bud growth. These processes include phosphoinositide (PI) signaling, Rho GTPase regulation of the actin cytoskeleton, and exocytosis. As yet, the interplay between these different processes is unclear, and two main models (Spatial Landmark and Allosteric Local Activation) have been proposed for Rho GTPase control of polarization in yeast. Here, we summarize the inter-relationship between these growth processes and present a more unified model, the Exocytic Signa... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2888769 Tue, 06 Oct 2009 23:00:00 +0100 2888769 http://www.medworm.com/index.php?rid=2866171&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19801189%26dopt%3DAbstract Authors: Lidke DS, Wilson BS Protein localization and dynamics both have important roles in cell signal transduction. Biochemical studies have elucidated many details about the chain of events in signal cascades, but the poor temporal resolution and absence of spatial localization in these conventional techniques make it difficult to determine the "where and when" of protein interactions. Over the past decade, imaging technologies and biological tools have developed to a point where many fundamental questions about protein activity can be addressed at the molecular level in living cells, revealing spatio-temporal information that is not provided by traditional biochemical assays. In this review, we illustrate the power of emerging fluorescence microscopy techniques to capture and quant... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2866171 Thu, 01 Oct 2009 23:00:00 +0100 2866171 http://www.medworm.com/index.php?rid=2866170&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19801190%26dopt%3DAbstract Authors: Hoogenraad CC, Bradke F Microtubules have been regarded as essential structures for stable neuronal morphology but new studies are highlighting their role in dynamic neuronal processes. Recent work demonstrates that the microtubule cytoskeleton has an active role during different phases of neuronal polarization - microtubules and their stability determine axon formation, they maintain the identity of axons and they regulate the dynamics of dendritic spines, the major sites of excitatory synaptic input. Although microtubules fulfill distinct cellular functions at different developmental stages, the underlying molecular mechanisms are remarkably similar. Reccurring themes are that microtubules direct specific membrane traffic and affect actin dynamics to locally organize axon gr... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2866170 Thu, 01 Oct 2009 23:00:00 +0100 2866170 http://www.medworm.com/index.php?rid=2859333&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19796946%26dopt%3DAbstract Authors: von Mikecz A Nuclear inclusions that contain proteins with expanded polyglutamine (polyQ) repeats are observed in neurodegenerative aggregation diseases and are, therefore, viewed as a pathologic feature. However, a summary of research indicates that polyQ repeats are inherently both toxic and functional at the same time. PolyQ motifs occur in proteins involved in gene expression and promote nuclear assemblies such as the transcription initiation complex. Transition of these functional complexes to insoluble protein aggregates is constitutively prevented by proteasomal proteolysis. Thus, conditions that exhaust the ubiquitin-proteasome system, such as the extensive production of expanded polyQ proteins, aging and xenobiotic stress, induce a congested state in which nuclear pro... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2859333 Mon, 28 Sep 2009 23:00:00 +0100 2859333 http://www.medworm.com/index.php?rid=2824943&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19766491%26dopt%3DAbstract Authors: Meves A, Stremmel C, Gottschalk K, Fässler R Kindlins are a group of proteins that have recently attracted attention for their ability to bind and activate integrins. Moreover, they have also been linked to inherited and acquired human diseases including Kindler syndrome, leukocyte adhesion deficiency, and cancer. Although most studies have focused on kindlins as key regulatory components of cell-extracellular matrix junctions such as focal adhesions, preliminary data suggest the involvement of additional cellular compartments in mediating their functions, particularly at cell-cell contacts and the nucleus. Investigating the many roles of kindlins is likely to expand and sharpen our view on the versatility of integrin-mediated cell adhesion, the nuclear function of focal ... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2824943 Wed, 16 Sep 2009 23:00:00 +0100 2824943 http://www.medworm.com/index.php?rid=2805227&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19758803%26dopt%3DAbstract Authors: Lai AZ, Abella JV, Park M The Met receptor tyrosine kinase (RTK) regulates several distinct biological processes, including cell scatter, cell invasion, cell survival and epithelial remodeling. MET is genetically altered through several mechanisms in multiple human cancers; these events are causally related to cancer initiation and progression, identifying Met as a potential therapeutic target. Recent evidence highlights additional roles for Met in cancer through crosstalk with other receptors and cell surface proteins. In this review, we discuss recent progress in our understanding of mechanisms of interaction between Met, the epidermal growth factor receptor family and other cell surface protein families, and how these contribute to signal crosstalk, oncogenesis and drug res... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2805227 Sun, 13 Sep 2009 23:00:00 +0100 2805227 http://www.medworm.com/index.php?rid=2800745&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19748270%26dopt%3DAbstract Authors: Lucas WJ, Ham BK, Kim JY Land plants have developed highly sophisticated intercellular channels called plasmodesmata (PD) that mediate the cell-to-cell trafficking of signaling molecules, including non-cell autonomous proteins (NCAPs) and RNAs. Until recently, the biological significance of this position-dependent intercellular signaling system was underestimated, as only a limited number of endogenous NCAPs had been discovered. However, identification of an ever-increasing population of NCAPs suggests that the PD communication pathway is involved in diverse biological processes, ranging from development to pathogen defense. The identification of components involved in plasmodesmal structure and associated signaling molecules is now yielding novel insights into the evolution a... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2800745 Wed, 09 Sep 2009 23:00:00 +0100 2800745 http://www.medworm.com/index.php?rid=2775432&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19734049%26dopt%3DAbstract Authors: Bollen M, Gerlich DW, Lesage B While the importance of protein kinases for the spatial and temporal control of mitotic events has long been recognized, mitotic phosphatases have only recently come into the limelight. It is now well established that protein phosphatases counteract mitotic kinases, so contributing to the generation of switch-like responses at mitotic stage transitions. In addition, the timely dephosphorylation of mitotic phosphoproteins by tightly regulated phosphatases is required for the assembly and stability of the mitotic spindle, the initiation of anaphase, and exit from mitosis. Mitotic phosphatases also emerge as effectors of the DNA damage and spindle assembly checkpoints. These new findings show that protein phosphatases regulate every step of mitosis ... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2775432 Thu, 03 Sep 2009 23:00:00 +0100 2775432 http://www.medworm.com/index.php?rid=2775435&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19733077%26dopt%3DAbstract Authors: Steigemann P, Gerlich DW The intercellular canal containing the midbody is one of the most prominent structures in dividing animal cells, yet its function in the completion of cytokinesis by abscission remains largely unknown. This is because of its small size, which makes it difficult to investigate the cytoskeletal and membrane dynamics underlying abscission by standard light microscopy. The advent of new fluorescent probes and imaging technologies, along with sophisticated perturbation tools, provides new possibilities to elucidate the molecular control of this essential cell biological process. Here we discuss the control of midbody assembly and current models for the mechanism of abscission in animal cells. We highlight new methodologies that will facilitate testing and r... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2775435 Tue, 01 Sep 2009 23:00:00 +0100 2775435 http://www.medworm.com/index.php?rid=2775434&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19733078%26dopt%3DAbstract Authors: Helming L, Gordon S Fusion of macrophages leads to the formation of osteoclasts in bone and of multinucleated giant cells in granulomas. The precise function of granuloma-associated multinucleates giant cells is not clear but substantial progress has recently been made in identifying the molecular machinery involved in macrophage fusion. Signaling processes mediated by DAP12 and STAT6 induce a fusion-competent status. Chemotaxis through CCL2, cell-cell adhesion mediated by E-cadherin, exposure of phosphatidylserine, lipid recognition by CD36 and cytoskeletal rearrangements depending on RAC1 are prerequisites for successful macrophage fusion. We review current knowledge on the molecular mediators of giant cell formation, compare giant cells with osteoclasts and highlight key ta... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2775434 Tue, 01 Sep 2009 23:00:00 +0100 2775434 http://www.medworm.com/index.php?rid=2775433&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19733079%26dopt%3DAbstract Authors: King JS, Insall RH Understanding cell migration is centrally important to modern cell biology. However, despite years of study, progress has been hindered by experimental limitations and the complexity of the process. This has led to the popularity of Dictyostelium discoideum, with its experimentally-friendly lifestyle and small, haploid genome, as a tool to dissect the pathways involved in migration. This humble amoeba is now established at the centre of dramatic changes in our understanding of cell movement. In this review we describe the recent reinterpretation of the role of phosphatidylinositol trisphosphate (PIP(3)) and other intracellular messengers that connect signalling and migration, and the transition to models of chemotaxis driven by multiple, intertwined signalli... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2775433 Tue, 01 Sep 2009 23:00:00 +0100 2775433 http://www.medworm.com/index.php?rid=2768667&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19726187%26dopt%3DAbstract Authors: Vellai T, Takács-Vellai K, Sass M, Klionsky DJ The accumulation of cellular damage is a feature common to all aging cells and leads to decreased ability of the organism to survive. The overall rate at which damage accumulates is influenced by conserved metabolic factors (longevity pathways and regulatory proteins) that control lifespan through adjusting mechanisms for maintenance and repair. Autophagy, the major catabolic process of eukaryotic cells that degrades and recycles damaged macromolecules and organelles, is implicated in aging and in the incidence of diverse age-related pathologies. Recent evidence has revealed that autophagic activity is required for lifespan extension in various long-lived mutant organisms, and that numerous autophagy-related genes or proteins... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2768667 Sun, 30 Aug 2009 23:00:00 +0100 2768667 http://www.medworm.com/index.php?rid=2752726&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19716303%26dopt%3DAbstract Authors: Andreassi C, Riccio A Translation of localized mRNA is a fast and efficient way of reacting to extracellular stimuli with the added benefit of providing spatial resolution to the cellular response. The efficacy of this adaptive response ultimately relies on the ability to express a particular protein at the right time and in the right place. Although mRNA localization is a mechanism shared by most organisms, it is especially relevant in highly polarized cells, such as differentiated neurons. 3'-Untranslated regions (3'UTRs) of mRNAs are critical both for the targeting of transcripts to specific subcellular compartments and for translational control. Here we review recent studies that indicate how, in response to extracellular cues, nuclear and cytoplasmic remodeling of the 3'U... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2752726 Tue, 25 Aug 2009 23:00:00 +0100 2752726 http://www.medworm.com/index.php?rid=2752725&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19716304%26dopt%3DAbstract Authors: Bryant C, Fitzgerald KA Germline-encoded pattern recognition receptors (PRRs) sense microbial or endogenous products released from damaged or dying cells and trigger innate immunity. In most cases, sensing of these signals is coupled to signal transduction pathways that lead to transcription of immune response genes that combat infection or lead to cell death. Members of the NOD-like receptor (NLR) family assemble into large multiprotein complexes, termed inflammasomes. Inflammasomes do not regulate transcription of immune response genes, but activate caspase-1, a proteolytic enzyme that cleaves and activates the secreted cytokines interleukin-1beta and interleukin-18. Inflammasomes also regulate pyroptosis, a caspase-1-dependent form of cell death that is highly inflammatory.... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2752725 Tue, 25 Aug 2009 23:00:00 +0100 2752725 http://www.medworm.com/index.php?rid=2752724&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19716305%26dopt%3DAbstract Authors: Giannone G, Mège RM, Thoumine O To trigger cell motility, forces generated by the cytoskeleton must be transmitted physically to the external environment through transmembrane adhesion molecules. One model put forward twenty years ago to describe this process is the molecular clutch by which a modular interface of adaptor proteins mediates a dynamic mechanical connection between the actin flow and cell adhesion complexes. Recent optical imaging experiments have identified key clutch molecules linked to specific chemical and mechanical signal transduction pathways, particularly regarding integrins in migrating cells, IgCAMs in neuronal growth cones, and cadherins at intercellular junctions. We propose here the concept of a multi-level clutch as a useful analogy to grasp th... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2752724 Tue, 25 Aug 2009 23:00:00 +0100 2752724 http://www.medworm.com/index.php?rid=2745918&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19713114%26dopt%3DAbstract Authors: Martin SG In many systems, microtubules contribute spatial information to cell morphogenesis, for instance in cell migration and division. In rod-shaped fission yeast cells, microtubules control cell morphogenesis by transporting polarity factors, namely the Tea1-Tea4 complex, to cell tips. This complex then recruits the DYRK kinase Pom1 to cell ends. Interestingly, recent work has shown that these proteins also provide long-range spatial cues to position the division site in the middle of the cell and temporal signals to coordinate cell length with the cell cycle. Here I review how these microtubule-associated proteins form polar morphogenesis centers that control and integrate both spatial and temporal aspects of cell morphogenesis. PMID: 19713114 [PubMed - as supplied b... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2745918 Mon, 24 Aug 2009 23:00:00 +0100 2745918 http://www.medworm.com/index.php?rid=2742272&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19709882%26dopt%3DAbstract Authors: Yáñez-Mó M, Barreiro O, Gordon-Alonso M, Sala-Valdés M, Sánchez-Madrid F Membrane lipids and proteins are non-randomly distributed and are unable to diffuse freely in the plane of the membrane. This is because of multiple constraints imposed both by the cortical cytoskeleton and by the preference of lipids and proteins to cluster into diverse and specialized membrane domains, including tetraspanin-enriched microdomains, glycosylphosphatidyl inositol-linked proteins nanodomains and caveolae, among others. Recent biophysical characterization of tetraspanin-enriched microdomains suggests that they might be specially suited for the regulation of avidity of adhesion receptors and the compartmentalization of enzymatic activities. Moreover, modulation by tetr... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2742272 Sun, 23 Aug 2009 23:00:00 +0100 2742272 http://www.medworm.com/index.php?rid=2742271&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19709883%26dopt%3DAbstract Authors: Pierres A, Monnet-Corti V, Benoliel AM, Bongrand P Cells sense physical properties of their environment including substratum rigidity, roughness, and topography of recognition sites. The cell surface displays continuous deformations of nanometer-scale amplitude and Hz frequency. Recent results support the hypothesis that these surface undulations constitute a powerful strategy for the rapid acquisition of environmental cues: transient contact with surroundings generates forces of piconewton intensity as a result of rapid formation and dissociation of intermolecular bonds. The combination of binding and steric forces is expected to drive conformational changes and lateral reorganization of membrane biomolecules, thus generating signaling cascades. We propose that spontaneous me... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2742271 Sun, 23 Aug 2009 23:00:00 +0100 2742271 http://www.medworm.com/index.php?rid=2730698&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19699642%26dopt%3DAbstract Authors: Brangwynne CP, Koenderink GH, Mackintosh FC, Weitz DA All substances exhibit constant random motion at the microscopic scale. This is a direct consequence of thermal agitation, and leads to diffusion of molecules and small particles in a liquid. In addition to this nondirected motion, living cells also use active transport mechanisms, such as motor activity and polymerization forces that depend on linear biopolymers and are therefore fundamentally directed in nature. Nevertheless, it has become increasingly clear that such active processes can also drive significant random fluctuations that can appear surprisingly like thermal diffusion of particles, but faster. Here, we discuss recent progress in quantifying this behavior and identifying its origins and consequences. We sugge... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2730698 Wed, 19 Aug 2009 23:00:00 +0100 2730698 http://www.medworm.com/index.php?rid=2675496&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19651513%26dopt%3DAbstract Authors: Zeke A, Lukács M, Lim WA, Reményi A Scaffold proteins influence cellular signalling by binding to multiple signalling enzymes, receptors or ion channels. Although normally devoid of catalytic activity, they have a big impact on controlling the flow of signalling information. By assembling signalling proteins into complexes, they play the part of signal processing hubs. As we learn more about the way signalling components are linked into natural signalling circuits, researchers are becoming interested in building non-natural signalling pathways to test our knowledge and/or to intentionally reprogram cellular behaviour. In this review, we discuss the role of scaffold proteins as efficient tools for assembling intracellular signalling complexes, both natural and artific... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2675496 Fri, 31 Jul 2009 23:00:00 +0100 2675496 http://www.medworm.com/index.php?rid=2669481&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19648010%26dopt%3DAbstract Authors: Kang JS, Liu C, Derynck R Transforming growth factor-beta (TGF-beta) regulates cell proliferation, differentiation and apoptosis, and TGF-beta-related proteins have key roles in development, tissue homeostasis and disease. Upon binding to their cell surface receptors, TGF-beta family proteins signal through Smads to induce changes in gene expression. TGF-beta-induced Smad signaling and additional non-Smad pathways have been studied extensively in an effort to understand the complex and versatile responses to TGF-beta family proteins. Recently, it has become increasingly apparent that the signaling responses are also extensively defined by regulatory mechanisms at the level of the receptors themselves. Here, we discuss recent insights into the effects of post-translational modi... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2669481 Thu, 30 Jul 2009 23:00:00 +0100 2669481 http://www.medworm.com/index.php?rid=2669480&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19648011%26dopt%3DAbstract Authors: Chariot A The IkappaB kinase (IKK) complex is involved in transcriptional activation by phosphorylating the inhibitory molecule IkappaBalpha, a modification that triggers its subsequent degradation, enabling activation of nuclear factor kappa B (NF-kappaB). Importantly, recent reports indicate that multiple cytoplasmic and nuclear proteins distinct from the NF-kappaB and IkappaB proteins are phosphorylated by the catalytic subunits of the IKK complex, IKKalpha or IKKbeta. Here, I describe how IKK subunits can have crucial roles in allergy, inflammation and immunity by targeting proteins such as SNAP23 and IRF7, but also in cancer by phosphorylating key molecules such as p53, TSC1 and FOXO3a through NF-kappaB-independent pathways. Thus, these recent findings considerably widen ... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2669480 Thu, 30 Jul 2009 23:00:00 +0100 2669480 http://www.medworm.com/index.php?rid=2646402&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19631546%26dopt%3DAbstract Authors: Feldman M, Gisou van der Goot F Proteins of the endomembrane system undergo assisted folding in the endoplasmic reticulum (ER), then quality-control and, if misfolded, ER-associated degradation (ERAD). Recent findings on the biogenesis of a type-I membrane protein (an LRP6 mutant) lead us to hypothesize the existence of a novel mechanism promoting folding of membrane proteins from the cytosolic side of the ER. The proposed folding mechanism involves cycles of chaperone binding through mono-ubiquitylation and de-ubiquitylation, followed eventually by poly-ubiquitylation and ERAD. This suggests a novel dual role for ubiquitylation in the ER - dependent on the type of ubiquitin chains involved - in folding and in degradation, and highlights the potential importance of de-ubiquity... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2646402 Tue, 21 Jul 2009 23:00:00 +0100 2646402 http://www.medworm.com/index.php?rid=2622343&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19616950%26dopt%3DAbstract Authors: Rino J, Carmo-Fonseca M In higher eukaryotes, the vast majority of protein-coding genes contain introns that must be removed from precursor mRNA (pre-mRNA) with great precision by the spliceosome. Spliceosomes are massive RNA-protein macromolecular machines with >100 distinct components that assemble onto nascent transcripts and are released from the mRNA after splicing. A large and longstanding body of biochemical evidence indicates that the spliceosome is constructed de novo for each round of splicing in an ordered piece-by-piece stepwise assembly. More recently, exciting advances in intracellular imaging approaches are providing new clues to understand the dynamic organization of this and other multi-component molecular machines in the nucleus. The emerging data suggest ... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2622343 Thu, 16 Jul 2009 23:00:00 +0100 2622343 http://www.medworm.com/index.php?rid=2622344&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19615906%26dopt%3DAbstract Authors: Parrinello S, Lloyd AC Dissecting the early steps of tumourigenesis is key to our understanding of cancer biology. However, lack of knowledge of initiating mutations and the target 'cell of origin' has slowed progress towards this goal. Genetically engineered mouse models of the tumour-predisposition syndrome neurofibromatosis type-1 provide a rare opportunity to study tumour initiation resulting from a known genetic change in a known cell type. Recent exciting work using these models now sheds more light onto early tumourigenesis. Here, we discuss the studies that have identified mature differentiated Schwann cells as the cell of origin and revealed the molecular and cellular mechanisms of neurofibroma initiation. A novel dual and opposing role for the microenvironment, from ... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2622344 Tue, 14 Jul 2009 23:00:00 +0100 2622344 http://www.medworm.com/index.php?rid=2592735&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19589679%26dopt%3DAbstract Authors: Lipps HJ, Rhodes D Although many biochemical and structural studies have demonstrated that DNA sequences containing runs of adjacent guanines spontaneously fold into G-quadruplex DNA structures in vitro, only recently has evidence started to accumulate for their presence and function in vivo. Genome-wide analyses have revealed that functional genomic regions from highly divergent organisms are enriched in DNA sequences with G-quadruplex-forming potential, suggesting that G-quadruplexes could provide a nucleic-acid-based mechanism for regulating telomere maintenance, as well as transcription, replication and translation. Here, we review recent studies aimed at uncovering the in vivo presence and function of G-quadruplexes in genomes and RNA, with a particular focus on telomeric... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2592735 Mon, 06 Jul 2009 23:00:00 +0100 2592735 http://www.medworm.com/index.php?rid=2580969&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19576775%26dopt%3DAbstract Authors: Lim HH, Zhang T, Surana U The assembly of a bipolar spindle is crucial for symmetric partitioning of duplicated chromosomes during cell division. Centrosomes (spindle pole body [SPB] in yeast) constitute the two poles of this bipolar structure and serve as microtubule nucleation centers. A eukaryotic cell enters the division cycle with one centrosome and duplicates it before spindle formation. A proteinaceous link keeps duplicated centrosomes together until it is severed at onset of mitosis, enabling centrosomes to migrate away from each other and assemble a characteristic mitotic spindle. Hence, centrosome separation is crucial in assembly of a bipolar spindle. Whereas centrosome (or SPB) duplication has been characterized in some detail, the separation process is less well u... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2580969 Tue, 30 Jun 2009 23:00:00 +0100 2580969 http://www.medworm.com/index.php?rid=2573580&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19570677%26dopt%3DAbstract Authors: Zyss D, Gergely F The regulation of centrosome number and function underlies bipolar mitotic spindle formation and genetic integrity. Cancer cells both in culture and in situ exhibit a wide range of centrosome abnormalities. Here, we briefly review advances in our understanding of the pathways that govern normal centrosome function and outline the potential causes and consequences of their deregulation in disease. There is ample observational but little experimental evidence to support the conventional model that centrosome dysfunction causes genomic instability and, as a result, cancer. This model has been challenged by recent studies that have uncovered evidence of a direct link between centrosome function in asymmetric cell division and tumourigenesis. Thus, it is timely to... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2573580 Sun, 28 Jun 2009 23:00:00 +0100 2573580 http://www.medworm.com/index.php?rid=2557047&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19560357%26dopt%3DAbstract Authors: Silverman MA, Leroux MR Cilia are organelles that project from most eukaryotic organisms and cell types. Their pervasiveness stems from having remarkably versatile propulsive and sensory functions, which in humans are recognized to have essential roles in physiology and development. Underappreciated, however, are their diverse ultrastructures and typically bipartite organization consisting of doublet and singlet microtubules. Moreover, the overall shapes of the membrane-ensheathed cilia are varied, as exemplified by differences between hair-like olfactory cilia and rod- or cone-shaped photoreceptor connecting cilia-outer segments. Although cell-specific transcriptional programs are evidently crucial in establishing ciliary morphological specialization, few players directly inv... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2557047 Wed, 24 Jun 2009 23:00:00 +0100 2557047 http://www.medworm.com/index.php?rid=2557046&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19560358%26dopt%3DAbstract Authors: Wu J, Mlodzik M Most epithelial cells, besides their ubiquitous apical-basal polarity, are polarized within the plane of the epithelium, which is called planar cell polarity (PCP). Using Drosophila as a model, meaningful progress has been made in the identification of key PCP factors and the dissection of their intracellular molecular interactions. The long-range, global aspects of coordinated polarization and the overlying regulatory mechanisms that create the initial polarity direction have, however, remained elusive. Several recent publications have outlined potential mechanisms of how the global regulation of PCP might be controlled and how the distinct core factor groups might interact via frizzled, Van Gogh or flamingo. This review focuses on these exciting features and ... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2557046 Wed, 24 Jun 2009 23:00:00 +0100 2557046 http://www.medworm.com/index.php?rid=2526684&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19540123%26dopt%3DAbstract Authors: Sann S, Wang Z, Brown H, Jin Y Membrane trafficking and cargo delivery are essential for axonal and dendritic growth and guidance. Neurons have numerous diverse post-Golgi vesicles and recent advances have clarified their identity and regulation. Combinatorial approaches using in vivo imaging of 'intracellular cargo address labels' and functional perturbation have provided insight into these processes. In particular, the UNC-51 kinase regulates the trafficking of early endosomes and their axon guidance molecular cargos in several types of neurons in multiple organisms. Vesicular compartments bearing features of recycling endosomes, late endosomes or lysosomes also contribute to membrane addition and protein trafficking during neurite outgrowth and extension. New work shows tha... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2526684 Tue, 16 Jun 2009 23:00:00 +0100 2526684 http://www.medworm.com/index.php?rid=2526687&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19524440%26dopt%3DAbstract Authors: Vallee RB, Seale GE, Tsai JW Motor proteins are involved in a wide range of cellular and subcellular movements. Recent studies have implicated two motor proteins in particular, myosin II and cytoplasmic dynein, in diverse aspects of cell migration. This review focuses on emerging roles for these proteins in the nervous system, with particular emphasis on migrating neurons and neuronal growth cones. The former cells exhibit unusual features of centrosome and nuclear movement, whereas growth cones offer an opportunity to evaluate motor protein function in a region of cytoplasm free of these organelles. PMID: 19524440 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2526687 Wed, 10 Jun 2009 23:00:00 +0100 2526687 http://www.medworm.com/index.php?rid=2526821&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19394225%26dopt%3DAbstract Authors: Guasconi V, Puri PL Muscle regeneration provides a paradigm by which to study how extrinsic signals coordinate gene expression in somatic stem cells (satellite cells) by directing the genome distribution of chromatin-modifying complexes. Understanding the signal-dependent control of the epigenetic events underlying the transition of muscle stem cells through sequential regeneration stages holds the promise to reveal new targets for selective interventions toward repairing diseased muscles. This review describes the latest findings on how regeneration cues are integrated at the chromatin level to build the transcription network that regulates progression of endogenous muscle progenitors throughout the myogenic program. In particular, we describe how specific epigenetic signatur... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2526821 Sun, 31 May 2009 23:00:00 +0100 2526821 http://www.medworm.com/index.php?rid=2526819&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19406642%26dopt%3DAbstract Authors: Qualmann B, Kessels MM Actin nucleators promote the polymerization of the different types of actin arrays formed in a variety of cellular processes, such as cell migration, cellular morphogenesis and membrane trafficking processes. Several novel nucleators have been discovered recently. They all contain Wiskott-Aldrich syndrome protein (WASP) homology 2 (WH2 or W) domains for actin nucleation but seem to employ different molecular mechanisms and serve distinct cellular functions. Here, we summarize what is currently known about the different molecular mechanisms that Spire, Cordon-Bleu and Leiomodin seem to use and, also, the bacterial counterparts that mimic them (VopF, VopL and TARP). Recent studies on these WH2 proteins offer unique insight into the biological problem of ac... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2526819 Sun, 31 May 2009 23:00:00 +0100 2526819 http://www.medworm.com/index.php?rid=2526816&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19406643%26dopt%3DAbstract Authors: Woolner S, Bement WM Unconventional myosins are proteins that bind actin filaments in an ATP-regulated manner. Because of their association with membranes, they have traditionally been viewed as motors that function primarily to transport membranous organelles along actin filaments. Recently, however, a wealth of roles for myosins that are not obviously related to organelle transport have been uncovered, including organization of F-actin, mitotic spindle regulation and gene transcription. Furthermore, it has also become apparent that the motor domains of different myosins vary strikingly in their biophysical attributes. We suggest that the assumption that most unconventional myosins function primarily as organelle transporters might be misguided. PMID: 19406643 [PubMed - i... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2526816 Sun, 31 May 2009 23:00:00 +0100 2526816 http://www.medworm.com/index.php?rid=2526760&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19409791%26dopt%3DAbstract Authors: Michalak M, Opas M The concept of the presence of sarcoplasmic reticulum (SR) membrane in the heart is widely accepted and has been considered merely to be a different name for the endoplasmic reticulum (ER) in muscle tissues. Cardiac SR membranes are specialized in the regulation of Ca(2+) transport and control of excitation-contraction coupling. By contrast, the ER is responsible for protein synthesis, modification, secretion, lipid and steroid synthesis, and modulation of Ca(2+) signaling. Recent developments have indicated that functional changes in proteins or pathways normally associated with ER and not SR membrane impact cardiac development and pathology. Here, we propose that the SR and ER might be functionally distinct internal membrane compartments in cardiomyocytes.... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2526760 Sun, 31 May 2009 23:00:00 +0100 2526760 http://www.medworm.com/index.php?rid=2526706&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19419870%26dopt%3DAbstract Authors: Wang X, Proud CG It is well established that the target of rapamycin (TOR) protein kinase has pivotal roles in controlling cell functions (including protein synthesis, cell growth and cell proliferation) and is implicated in numerous human diseases. Mammalian TOR complex 1 (mTORC1) signalling is activated by hormones and growth factors, and is also stimulated by intracellular amino acids. Recent research has provided important new insight into the poorly understood mechanism by which amino acids activate mTORC1 signalling, showing that the protein kinase MAP4K3 and Rag GTPases have important roles in this. mTORC1 is known to control the G1/S transition of the cell cycle: new data show that (m)TORC1 also controls G2/M progression in yeast and mammals, albeit in contrasting ways... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2526706 Sun, 31 May 2009 23:00:00 +0100 2526706 http://www.medworm.com/index.php?rid=2526702&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19428253%26dopt%3DAbstract Authors: Wang KC, Helms JA, Chang HY Hox genes encode transcription factors that specify embryonic positional identity in cells and guide tissue differentiation. Recent advances have greatly increased our understanding of the epigenetic mechanisms that ensure the faithful expression of Hox genes in adult cells and which involve the interplay of histone methylation, demethylation and intergenic transcription of long non-coding RNAs. The transcriptional memory of Hox genes poses both an opportunity and a challenge for regenerative medicine. Matching the positional identity of transplanted stem cells with that of the host environment, as reflected by their respective Hox profiles, is likely to be required to achieve regenerative healing. Strategies to manipulate the plasticity of Hox gene... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2526702 Sun, 31 May 2009 23:00:00 +0100 2526702 http://www.medworm.com/index.php?rid=2526828&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19345106%26dopt%3DAbstract Authors: McClatchey AI, Fehon RG Recent studies highlight the importance of the distribution of membrane receptors in controlling receptor output and in contributing to complex biological processes. The cortical cytoskeleton is known to affect membrane protein distribution but the molecular basis of this is largely unknown. Here, we discuss the functions of Merlin and the ERM proteins both in linking membrane proteins to the underlying cortical cytoskeleton and in controlling the distribution of and signaling from membrane receptors. We also propose a model that could account for the intricacies of Merlin function across model organisms. PMID: 19345106 [PubMed - indexed for MEDLINE] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2526828 Thu, 30 Apr 2009 23:00:00 +0100 2526828 http://www.medworm.com/index.php?rid=2526824&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19359177%26dopt%3DAbstract Authors: Twiss JL, Fainzilber M Decades of controversy regarding ribosome occurrence in axons are finally coalescing to a realization that the protein synthesis machinery is recruited and activated in both central and peripheral axons during development and in adult peripheral axons upon injury. Exciting recent findings indicate that ribosome recruitment to axons occurs via lateral transfer from glial cells, a mechanism that could be part of a continuum of intercellular communication systems including tunneling nanotubes and exosomes. Such transcellular interactions could have crucial roles in nervous system functions and will provide new avenues for research into long-standing problems. PMID: 19359177 [PubMed - indexed for MEDLINE] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2526824 Thu, 30 Apr 2009 23:00:00 +0100 2526824 http://www.medworm.com/index.php?rid=2301133&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19342239%26dopt%3DAbstract Authors: van Attikum H, Gasser SM Chromatin structure has a crucial role in processes of metabolism, including transcription, DNA replication and DNA damage repair. An evolutionarily conserved variant of histone H2A, called H2AX, is one of the key components of chromatin. H2AX becomes rapidly phosphorylated on chromatin surrounding DNA double-strand breaks (DSBs). Recent studies have shown that H2AX and other components of damaged chromatin also become modified by acetylation and ubiquitylation. This review discusses how specific combinations of histone modifications affect the accumulation and function of DNA repair factors (MDC1, RNF8, RNF168, 53BP1, BRCA1) and chromatin remodeling complexes (INO80, SWR1, TIP60-p400) at DSBs. These collectively regulate DSB repair and checkpoint arre... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2301133 Tue, 31 Mar 2009 04:00:00 +0100 2301133 http://www.medworm.com/index.php?rid=2301127&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19342240%26dopt%3DAbstract Authors: Monshausen GB, Gilroy S Owing to the sessile nature of their lifestyle, plants have to respond to a wide range of signals, such as the force of the wind or the impedance of the soil, to entrain their development to prevailing environmental conditions. Indeed, mechanically responsive growth has been documented in plants for many years but new work on lateral root formation strongly supports the idea that biophysical forces can elicit complete de novo developmental programs. In addition, only recently have molecular candidates for plant mechanosensors emerged. Such advances in understanding plant mechanoresponsive development have relied heavily on comparison with mechanosensors characterized in organisms such as Saccharomyces cerevisiae and Escherichia coli, but key questions r... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2301127 Tue, 31 Mar 2009 04:00:00 +0100 2301127 http://www.medworm.com/index.php?rid=2301141&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19328693%26dopt%3DAbstract Authors: Benayoun BA, Veitia RA Cellular responses to environmental or physiological cues rely on transduction pathways that must ensure discrimination between different signals. These cascades 'crosstalk' and lead to a combinatorial regulation. This often results in different combinations of post-translational modifications (PTMs) on target proteins, which might act as a molecular barcode. Although appealing, the idea of the existence of such a code for transcription factors is debated. Using general arguments and recent evidence, we propose that a PTM code is not only possible but necessary in the context of transcription factors regulating multiple processes. Thus, the coding potential of PTM combinations should both provide a further layer of information integration from several tr... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2301141 Thu, 26 Mar 2009 04:00:00 +0100 2301141 http://www.medworm.com/index.php?rid=2301139&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19328694%26dopt%3DAbstract Authors: Newpher TM, Ehlers MD Changes in the molecular composition and signaling properties of excitatory glutamatergic synapses onto dendritic spines mediate learning-related plasticity in the mammalian brain. This molecular adaptation serves as the most celebrated cell biological model for learning and memory. Within their micron-sized dimensions, dendritic spines restrict the diffusion of signaling molecules and spatially confine the activation of signal transduction pathways. Much of this local regulation occurs by spatial compartmentalization of glutamate receptors. Here, we review recently identified cell biological mechanisms regulating glutamate receptor mobility within individual dendritic spines. We discuss the emerging functions of glutamate receptors residing within sub-sp... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2301139 Thu, 26 Mar 2009 04:00:00 +0100 2301139 http://www.medworm.com/index.php?rid=2275202&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19285866%26dopt%3DAbstract Authors: Frühbeck G, Sesma P, Burrell MA Both brown and white adipocytes were previously considered to be derived from the same precursor cell, despite being histologically and functionally different. However, a recent study shows that overexpression of the transcriptional regulator positive regulatory domain containing 16 (PRDM16) determines the development of brown adipocytes from a progenitor that expresses myoblast markers. Surprisingly, loss of PRDM16 from these precursors does not lead to white adipocyte differentiation. Thus, PRDM16 controls a bidirectional cell fate switch between skeletal myoblasts and brown adipocytes. PMID: 19285866 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2275202 Thu, 12 Mar 2009 04:00:00 +0100 2275202 http://www.medworm.com/index.php?rid=2275201&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19285867%26dopt%3DAbstract Authors: Müller S, Wright AJ, Smith LG Unique mechanisms are used to orient cell division planes in plants. A cortical ring of cytoskeletal filaments called the preprophase band (PPB) predicts the future division plane during G2 and is disassembled as the mitotic spindle forms, leaving behind a 'cortical division site' (CDS) that guides the placement of the new cell wall (cell plate) during cytokinesis. The molecular features of the CDS have remained elusive for decades. Recently, a few proteins have at last been identified that are specifically localized to or excluded from the CDS and that participate in the orientation, attachment or maturation of cell plates. Recent progress has also been made in identifying proteins needed for PPB formation and thus for division plane establi... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2275201 Thu, 12 Mar 2009 04:00:00 +0100 2275201 http://www.medworm.com/index.php?rid=2275200&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19285868%26dopt%3DAbstract Authors: von Dassow G Animal cells are deformable, yet live together bound into tissues. Consequently, physical perturbations imposed by neighbors threaten to disrupt the spatial coordination of cell cleavage with chromosome segregation during mitosis. Emerging evidence demonstrates that animal cells integrate multiple positional cues during cleavage-furrow induction, perhaps to facilitate error correction. Classical work indicated that the asters provide the stimulus for furrow induction, but recent results implicate the central spindle at least as much. Similarly, although classical work concluded that the stimulus occurs at the cell equator, new evidence shows that asters modulate cortical contractility outside the equator as well. Meanwhile, a newly revealed distinction between sta... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2275200 Thu, 12 Mar 2009 04:00:00 +0100 2275200 http://www.medworm.com/index.php?rid=2275199&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19285869%26dopt%3DAbstract Authors: Kunda P, Baum B The most dramatic changes in eukaryotic cytoskeletal organization and dynamics occur during passage through mitosis. Although both spindle self-organization and actin-dependent cytokinesis have long been the subject of intense investigation, it has only recently become apparent that the actin cortex also has a key role during early mitosis. This is most striking in animal cells, in which changes in the actin cytoskeleton drive mitotic cell rounding and cortical stiffening. This mitotic cortex then functions as a foundation for spindle assembly and to guide spindle orientation with respect to extracellular chemical and mechanical cues. Here, we discuss this recent work and the possible role of crosstalk between the mitotic actin cortex and the plus ends of astra... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2275199 Thu, 12 Mar 2009 04:00:00 +0100 2275199 http://www.medworm.com/index.php?rid=2261281&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19269181%26dopt%3DAbstract Authors: Caviston JP, Holzbaur EL The neurodegenerative disorder Huntington's disease is caused by an expansion in the polyglutamine repeat region of the protein huntingtin. Multiple studies in cellular and animal model systems indicate that this mutation imparts a novel toxic function required for disease pathogenesis. However, the normal function of huntingtin, an essential cellular protein in higher vertebrates, is not yet well understood. Emerging data indicate an important role for wild-type huntingtin in the intracellular transport of vesicles and organelles. Here, we discuss current progress on the role of huntingtin in vesicular trafficking, focusing on the proposal that huntingtin might be a crucial regulator of organelle transport along the cellular cytoskeleton. PMID: 19... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2261281 Thu, 05 Mar 2009 05:00:00 +0100 2261281 http://www.medworm.com/index.php?rid=2234158&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19251418%26dopt%3DAbstract Authors: Mili S, Macara IG Cell polarization relies on the asymmetric organization of cellular structures and activities, and is fundamentally important both during development and for the proper function of most somatic cells. Asymmetries in the distribution and activity of proteins can be achieved through localization of RNA molecules that usually give rise to proteins at specific subcellular sites. It is increasingly appreciated that this is a widely used mechanism affecting protein function at multiple levels. The description of a new RNA localization pathway involving the tumor-suppressor protein APC raises questions regarding coordination between distinct localization pathways and their effects on protein function and cell polarity. PMID: 19251418 [PubMed - as supplied by pub... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2234158 Fri, 27 Feb 2009 05:00:00 +0100 2234158 http://www.medworm.com/index.php?rid=2191209&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19217783%26dopt%3DAbstract Authors: Broemer M, Meier P Ubiquitin is a protein modifier that is conjugated to target proteins either as a single moiety or as polyubiquitin chains. Over the past several years, an increasing number of ubiquitin ligases and ubiquitin-deconjugating enzymes have been identified; these modulate cell survival by degradative and non-degradative means. Mutations that affect ubiquitin-mediated signalling are tightly linked to various human pathologies including tumorigenesis. Unravelling how the ubiquitin-signal is conjugated, edited and 'read' is crucial to understanding cellular processes such as endocytic trafficking, NF-kappaB signalling, gene expression, DNA repair and apoptosis. In this review, we summarize recent advances that start to elucidate how the ubiquitin message is used as ... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2191209 Thu, 12 Feb 2009 05:00:00 +0100 2191209 http://www.medworm.com/index.php?rid=2183320&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19208479%26dopt%3DAbstract Authors: Kikuchi A, Yamamoto H, Sato A Wnts comprise a large family of secreted, hydrophobic glycoproteins that control a variety of developmental and adult processes in all metazoan organisms, including cellular proliferation, differentiation, migration and polarity. Wnts have many receptors that are present on a variety of cell types, partly specifying which Wnt pathways are activated. Recently, evidence has been accumulating that specificity of activation downstream of Wnt is also regulated by receptor-mediated endocytosis and the presence of cofactors such as heparan sulfate proteoglycans, in addition to the formation of specific ligand-receptor pairs. Here, we describe how the different endocytic routes of Wnt receptors through caveolin and clathrin determine specificity of Wnt si... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2183320 Sat, 07 Feb 2009 05:00:00 +0100 2183320 http://www.medworm.com/index.php?rid=2173560&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19201609%26dopt%3DAbstract Authors: Lammens T, Li J, Leone G, De Veylder L As major regulators of the cell cycle, apoptosis and differentiation, E2F transcription factors have been studied extensively in a broad range of organisms. The recent identification of atypical E2F family members further expands our structural, functional and molecular view of the cellular E2F activity. Unlike other family members, atypical E2Fs have a duplicated DNA-binding domain and control gene expression without heterodimerization with dimerization partner proteins. Recently, knockout strategies in plants and mammals have pinpointed that atypical E2Fs have a crucial role in plant cell size control, endocycle regulation, proliferation and apoptotic response upon DNA stress. Their position at the crossroads of proliferation and DNA st... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2173560 Fri, 06 Feb 2009 05:00:00 +0100 2173560 http://www.medworm.com/index.php?rid=2173561&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19200729%26dopt%3DAbstract We present evidence that similar intracellular signaling principles underlying cytoskeletal regulation are used to control neural and vascular guidance, although the specific molecules used in neurons and endothelial cells are often different. PMID: 19200729 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2173561 Wed, 04 Feb 2009 05:00:00 +0100 2173561 http://www.medworm.com/index.php?rid=2138283&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19168356%26dopt%3DAbstract Authors: Clarke PR, Allan LA Cells respond to DNA damage or defects in the mitotic spindle by activating checkpoints that arrest the cell cycle. Alternatively, damaged cells can undergo cell death by the process of apoptosis. The correct balance between these pathways is important for the maintenance of genomic integrity while preventing unnecessary cell death. Although the molecular mechanisms of the cell cycle and apoptosis have been elucidated, the links between them have not been clear. Recent work, however, indicates that common components directly link the regulation of apoptosis with cell-cycle checkpoints operating during interphase, whereas in mitosis, the control of apoptosis is directly coupled to the cell-cycle machinery. These findings shed new light on how the balance bet... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2138283 Fri, 23 Jan 2009 05:00:00 +0100 2138283 http://www.medworm.com/index.php?rid=2110917&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19144519%26dopt%3DAbstract Authors: Hayashi T, Rizzuto R, Hajnoczky G, Su TP The physical association between the endoplasmic reticulum (ER) and mitochondria, which is known as the mitochondria-associated ER membrane (MAM), has important roles in various cellular 'housekeeping' functions including the non-vesicular transports of phospholipids. It has recently become clear that the MAM also enables highly efficient transmission of Ca(2+) from the ER to mitochondria to stimulate oxidative metabolism and, conversely, might enable the metabolically energized mitochondria to regulate the ER Ca(2+) homeostasis. Recent studies have shed light on molecular chaperones such as calnexin, calreticulin, ERp44, ERp57, grp75 and the sigma-1 receptor at the MAM, which regulate the association between the two organelles. The MAM... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2110917 Mon, 12 Jan 2009 05:00:00 +0100 2110917 http://www.medworm.com/index.php?rid=2110916&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19144520%26dopt%3DAbstract Authors: Cocucci E, Racchetti G, Meldolesi J The small vesicles shed from the surface of many cells upon stimulation, considered for a long time to be artefacts, are now recognized as specific structures that are distinct from the exosomes released upon exocytosis of multivesicular bodies. Recent reports indicate that shedding vesicles participate in important biological processes, such as the surface-membrane traffic and the horizontal transfer of protein and RNAs among neighboring cells, which are necessary for the rapid phenotype adjustments in a variety of conditions. In addition, shedding vesicles have important physiological and pathological roles: in coagulation, by mediating the coordinate contribution of platelets, macrophages and neutrophils; in inflammatory diseases, via the... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2110916 Mon, 12 Jan 2009 05:00:00 +0100 2110916 http://www.medworm.com/index.php?rid=2110915&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19144521%26dopt%3DAbstract Authors: Matozaki T, Murata Y, Okazawa H, Ohnishi H Signal regulatory protein (SIRP)alpha, also known as SHPS-1 or SIRPA, is a transmembrane protein that binds to the protein tyrosine phosphatases SHP-1 and SHP-2 through its cytoplasmic region and is predominantly expressed in neurons, dendritic cells and macrophages. CD47, a widely expressed transmembrane protein, is a ligand for SIRPalpha, with the two proteins constituting a cell-cell communication system. The interaction of SIRPalpha with CD47 is important for the regulation of migration and phagocytosis. Recent studies have implicated the CD47-SIRPalpha signalling pathway in immune homeostasis and in regulation of neuronal networks. Advances in the structural and functional analyses of the CD47-SIRPalpha signalling pathway now pro... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2110915 Mon, 12 Jan 2009 05:00:00 +0100 2110915 http://www.medworm.com/index.php?rid=2110914&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19144522%26dopt%3DAbstract Authors: Wasteneys GO, Ambrose JC The shape of plant cells depends on cortical microtubules. Their freedom from central microtubule organizing centres provides a powerful experimental system to study microtubule self-organization. New ideas have emerged from live-cell imaging of microtubules, particularly in the model system Arabidopsis thaliana, revealing the importance of encounters between microtubules in driving self-organization. Encounters are modulated by intrinsic microtubule-assembly dynamics, along with polymer activities that include cortical attachment, bundling and severing. Balancing the activities of microtubule-associated proteins (such as MOR1, CLASP, MAP65s and katanins) that control these processes is crucial for fine-tuning the organization of microtubule arrays. To... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2110914 Mon, 12 Jan 2009 05:00:00 +0100 2110914 http://www.medworm.com/index.php?rid=2075281&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19112021%26dopt%3DAbstract Authors: Prahlad V, Morimoto RI All cells possess surveillance and homeostatic mechanisms to adjust protein biogenesis to the demands of growth, differentiation, ageing and environmental stress. However, under certain circumstances, these mechanisms fail to adequately respond to proteotoxic imbalances and result in the accumulation of misfolded proteins. In humans, this can lead to neurodegeneration and other protein conformational diseases. To protect itself, the cell employs highly conserved stress responses and chaperone networks to maintain protein-folding homeostasis (proteostasis). Although the regulation of stress responses, such as the heat-shock response, and of proteostasis have been widely considered to be cell autonomous, recent studies using Caenorhabditis elegans have sho... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2075281 Fri, 26 Dec 2008 05:00:00 +0100 2075281 http://www.medworm.com/index.php?rid=2053401&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19091567%26dopt%3DAbstract Authors: Singhvi A, Garriga G Asymmetric cell division (ACD) is a fundamental process used to generate cell diversity during metazoan development that occurs when a cell divides to generate daughter cells adopting distinct fates. Stem cell divisions, for example, are a type of ACD and provide a source of new cells during development and in adult animals. Some ACDs produce a daughter cell that dies. In many cases, the reason why a cell divides to generate a dying daughter remains elusive. It was shown recently that denatured proteins are segregated asymmetrically during cell division. Here, we review data that provide interesting insights into how apoptosis is regulated during ACD and speculate on potential connections between ACD-induced cell death and partitioning of denatured protein... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2053401 Mon, 15 Dec 2008 05:00:00 +0100 2053401 http://www.medworm.com/index.php?rid=2028085&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19062290%26dopt%3DAbstract Authors: Rajyaguru P, Parker R Development requires the translation of stored maternal messenger RNAs (mRNAs) in a spatial and temporally specified manner. Maternal mRNAs are often in large RNA-protein (RNP) granules. Recent papers reveal that maternal mRNA granules in Caenorhabditis elegans oocytes and early development are dynamic and related to P-bodies and stress granules, which are conserved RNP granules seen in somatic cells. In addition, a highly conserved putative RNA helicase, termed CGH-1 in C. elegans, is now shown to be important for both for translation repression and the stability of stored mRNAs. The analysis of CGH-1 ortholog functions in somatic cells and its interacting proteins indicate possible mechanisms by which this protein family might stabilize stored maternal ... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=2028085 Wed, 03 Dec 2008 05:00:00 +0100 2028085 http://www.medworm.com/index.php?rid=1991804&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19027299%26dopt%3DAbstract Authors: Morrison DK The highly conserved 14-3-3 protein family has risen to a position of importance in cell biology owing to its involvement in vital cellular processes, such as metabolism, protein trafficking, signal transduction, apoptosis and cell-cycle regulation. The 14-3-3 proteins are phospho-serine/phospho-threonine binding proteins that interact with a diverse array of binding partners. Because many 14-3-3 interactions are phosphorylation-dependent, 14-3-3 has been tightly integrated into the core phospho-regulatory pathways that are crucial for normal growth and development and that often become dysregulated in human disease states such as cancer. This review examines the recent advances that further elucidate the role of 14-3-3 proteins as integrators of diverse signaling ... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1991804 Thu, 20 Nov 2008 05:00:00 +0100 1991804 http://www.medworm.com/index.php?rid=1991803&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19027300%26dopt%3DAbstract Authors: Corpet A, Almouzni G Understanding the basic mechanisms underlying chromatin dynamics during DNA replication in eukaryotic cells is of fundamental importance. Beyond DNA compaction, chromatin organization represents a means to regulate genome function. Thus, the inheritance and maintenance of the DNA sequence, along with its organization into chromatin, is central for eukaryotic life. To orchestrate DNA replication in the context of chromatin is a challenge, both in terms of accessibility to the compact structures and maintenance of chromatin organization. To meet the challenge of maintenance, cells have evolved efficient nucleosome dynamics involving assembly pathways and chromatin maturation mechanisms that restore chromatin organization in the wake of DNA replication. In th... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1991803 Thu, 20 Nov 2008 05:00:00 +0100 1991803 http://www.medworm.com/index.php?rid=1969505&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19010680%26dopt%3DAbstract Authors: Vestweber D, Winderlich M, Cagna G, Nottebaum AF The regulation of endothelial cell contacts is of central importance for the barrier function of the blood vessel wall and for the control of leukocyte extravasation. In addition, the plasticity of endothelial cell contacts is regulated during angiogenesis by growth factors, such as vascular endothelial growth factor and angiopoietin-1. Despite the participation of several adhesion molecules and receptors in the control of endothelial cell contacts, most of the currently known mechanisms involve vascular endothelial cadherin (VE-cadherin), an essential adhesion molecule for the stability of endothelial junctions. Here, we focus on recent results showing how leukocytes and angiogenic factors regulate endothelial junctions. PM... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1969505 Fri, 14 Nov 2008 05:00:00 +0100 1969505 http://www.medworm.com/index.php?rid=1911703&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18951795%26dopt%3DAbstract Authors: Carlucci A, Lignitto L, Feliciello A Mitochondria are highly specialized organelles and major players in fundamental aspects of cell physiology. In yeast, energy metabolism and coupling of mitochondrial activity to growth and survival is controlled by the protein kinase A pathway. In higher eukaryotes, modulation of the so-called A-kinase anchor protein (AKAP) complex regulates mitochondrial dynamics and activity, adapting the oxidative machinery and the metabolic pathway to changes in physiological demand. Protein kinases and phosphatases are assembled by AKAPs within transduction units, providing a mechanism to control signaling events at mitochondria and other target organelles. Ubiquitin-mediated proteolysis of signal transducers and effectors provides an additional layer ... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1911703 Thu, 23 Oct 2008 04:00:00 +0100 1911703 http://www.medworm.com/index.php?rid=1911702&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18951796%26dopt%3DAbstract Authors: Quinn CC, Wadsworth WG A network of connections is established as neural circuits form between neurons. To make these connections, neurons initiate asymmetric axon outgrowth in response to extracellular guidance cues. Within the specialized growth cones of migrating axons, F-actin and microtubules asymmetrically accumulate where an axon projects forward. Although many guidance cues, receptors and intracellular signaling components that are required for axon guidance have been identified, the means by which the asymmetry is established and maintained is unclear. Here, we discuss recent studies in invertebrate and vertebrate organisms that define a signaling module comprising UNC-6 (the Caenorhabditis elegans ortholog of netrin), UNC-40 (the C. elegans ortholog of DCC), PI3K, Ra... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1911702 Thu, 23 Oct 2008 04:00:00 +0100 1911702 http://www.medworm.com/index.php?rid=1911701&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18951797%26dopt%3DAbstract Authors: Ma H, Pederson T Nucleostemin (NS) is a protein concentrated in the nucleolus of most stem cells and also in many tumor cells, which has been implicated in cell-cycle progression owing to its ability to modulate p53. Depletion of NS causes G(1) cell-cycle arrest, but its overexpression does so as well. Recently, this paradox has been clarified. NS overexpression causes a sequestration of murine double minute 2 (MDM2), preventing the destruction of p53. A recent study has demonstrated that loss of NS promotes the interaction of L5 and L11 ribosomal proteins with MDM2 and, thus, also prevents p53 degradation. This new finding expands our understanding of the multiple modes of NS action and reinforces the concept that the nucleolus has key roles in cell-cycle progression. PMI... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1911701 Thu, 23 Oct 2008 04:00:00 +0100 1911701 http://www.medworm.com/index.php?rid=1911700&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18951798%26dopt%3DAbstract Authors: Bratman SV, Chang F The dynamics of microtubules (MTs) are crucial to many of their functions. Certain MT structures, such as the mitotic spindle apparatus, exhibit high MT turnover yet maintain their mass stably through long periods of time. Here, we highlight what are emerging as two important mechanisms for maintaining MT bundles: the first, MT nucleation from pre-existing MTs by means of gamma-tubulin-containing complexes; and the second, MT 'rescue' by the stabilizing protein CLASP. As examples, we describe recent advances in understanding the assembly and maintenance of simple MT bundles in fission yeast and plant cells, which have implications for the bundles of the animal mitotic spindle. PMID: 18951798 [PubMed - as supplied by publisher] (Source: Trends in Cell Bi... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1911700 Thu, 23 Oct 2008 04:00:00 +0100 1911700 http://www.medworm.com/index.php?rid=1873279&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18848778%26dopt%3DAbstract Authors: Green JL, Kuntz SG, Sternberg PW Receptor tyrosine kinase-like orphan receptor (Ror) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including skeletal and neuronal development, cell movement and cell polarity. Although Ror proteins were originally named because the associated ligand and signaling pathway were unknown, recent studies in multiple species have now established that Ror proteins are Wnt receptors. Depending on the cellular context, Ror proteins can either activate or repress transcription of Wnt target genes and can modulate Wnt signaling by sequestering Wnt ligands. New evidence implicates Ror proteins in planar cell polarity, an alternative Wnt pathway. Here, we review the progress made in understanding these... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1873279 Thu, 09 Oct 2008 04:00:00 +0100 1873279 http://www.medworm.com/index.php?rid=1873283&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18848448%26dopt%3DAbstract Authors: Brocardo M, Henderson BR The adenomatous polyposis coli (APC) tumor suppressor is a multi-functional protein, the mutation of which triggers colon cancer progression through de-regulation of the canonical Wnt signaling pathway and disruption of the mitotic spindle checkpoint. In recent years, APC has been detected at several unexpected intracellular locations, implicating APC in multiple roles that now include the regulation of directed cell migration, apoptosis and DNA repair. In this review, we discuss the intracellular trafficking pathway of APC and describe how truncated cancer-mutant forms of APC display frequent changes in sub-cellular localization and function. The transport routes of APC overlap that of other tumor suppressors, including BRCA1 and p53, pin-pointing com... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1873283 Wed, 08 Oct 2008 04:00:00 +0100 1873283 http://www.medworm.com/index.php?rid=1873282&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18848449%26dopt%3DAbstract Authors: Li WX Aberrant activation of the JAK-STAT pathway has been implicated in many human cancers. It has widely been assumed that the effects of STAT activation are mediated by direct transcriptional induction of STAT target genes. However, recent findings in Drosophila have identified a non-canonical mode of JAK-STAT signaling, which directly controls heterochromatin stability. This indicates that the JAK-STAT pathway also controls cellular epigenetic status, which affects expression of genes beyond those under direct STAT transcriptional control. Given the evolutionary conservation of the canonical pathway among different species, the non-canonical mode of JAK-STAT signaling might also operate in vertebrates. In this review, canonical versus non-canonical JAK-STAT signaling and t... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1873282 Wed, 08 Oct 2008 04:00:00 +0100 1873282 http://www.medworm.com/index.php?rid=1873281&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18848450%26dopt%3DAbstract Authors: Rowe RG, Weiss SJ The basement membrane (BM), a specialized network of extracellular matrix macromolecules, surrounds epithelial, endothelial, muscle, fat and nerve cells. During development, immune surveillance and disease states ranging from cancer to fibrosis, host cells penetrate the BM by engaging tissue-invasive programs, the identity of which remain largely undefined. Although it is commonly assumed that all cells employ similar mechanisms to cross BM barriers, accumulating evidence indicates that cells might selectively mobilize protease-dependent or -independent invasion programs. New data indicate that protease-dependent transmigration is largely reliant on a group of membrane-anchored metalloenzymes, termed the membrane-type matrix metalloproteinases, which irrevers... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1873281 Wed, 08 Oct 2008 04:00:00 +0100 1873281 http://www.medworm.com/index.php?rid=1873280&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18848451%26dopt%3DAbstract Authors: Idone V, Tam C, Andrews NW Ca(2+) influx through plasma membrane wounds triggers a rapid-repair response that is essential for cell survival. Earlier studies showed that repair requires the exocytosis of intracellular vesicles. Exocytosis was thought to promote resealing by 'patching' the plasma membrane lesion or by facilitating bilayer restoration through reduction in membrane tension. However, cells also rapidly repair lesions created by pore-forming proteins, a form of injury that cannot be resealed solely by exocytosis. Recent studies indicate that, in cells injured by pores or mechanical abrasions, exocytosis is followed by lesion removal through endocytosis. Describing the relationship between wound-induced exocytosis and endocytosis has implications for the understandi... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1873280 Wed, 08 Oct 2008 04:00:00 +0100 1873280 http://www.medworm.com/index.php?rid=1841393&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18824354%26dopt%3DAbstract Authors: Kunkel TA, Burgers PM Efficient and accurate replication of the eukaryotic nuclear genome requires DNA polymerases (Pols) alpha, delta and varepsilon. In all current replication fork models, polymerase alpha initiates replication. However, several models have been proposed for the roles of Pol delta and Pol varepsilon in subsequent chain elongation and the division of labor between these two polymerases is still unclear. Here, we revisit this issue, considering recent studies with diagnostic mutator polymerases that support a model wherein Pol varepsilon is primarily responsible for copying the leading-strand template and Pol delta is primarily responsible for copying the lagging-strand template. We also review earlier studies in light of this model and then consider prospects... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1841393 Fri, 26 Sep 2008 04:00:00 +0100 1841393 http://www.medworm.com/index.php?rid=1837604&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18819800%26dopt%3DAbstract Authors: Vladar EK, Axelrod JD Some epithelia contain cells with multiple motile cilia that beat in a concerted manner. New tools and experimental systems have facilitated molecular studies of cilium biogenesis and the coordinated planar polarization of cilia that leads to their concerted motility. A recent elegant study using embryonic frog epidermis demonstrates that Dishevelled, a key regulator of both the Wnt-beta-catenin and planar cell polarity pathways, controls both the docking and planar polarization of ciliary basal bodies. PMID: 18819800 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1837604 Wed, 24 Sep 2008 04:00:00 +0100 1837604 http://www.medworm.com/index.php?rid=1815989&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18805009%26dopt%3DAbstract Authors: Polager S, Ginsberg D The retinoblastoma tumor suppressor, pRb, restricts cell-cycle progression mainly by regulating members of the E2F-transcription-factor family. The Rb pathway is often inactivated in human tumors, resulting in deregulated-E2F activity that promotes proliferation or cell death, depending on the cellular context. Specifically, the outcome of deregulated-E2F activity is determined by integration of signals coming from the cellular DNA and the external environment. Alterations in cell proliferation and cell-death pathways are key features of transformed cells and, therefore, an understanding of the variables that determine the outcome of E2F activation is pivotal for cancer research and treatment. In this review, we discuss recent studies that have elucidated... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1815989 Thu, 18 Sep 2008 04:00:00 +0100 1815989 http://www.medworm.com/index.php?rid=1790615&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18786826%26dopt%3DAbstract Authors: D'Angelo MA, Hetzer MW Nuclear pore complexes are large aqueous channels that penetrate the nuclear envelope, thereby connecting the nuclear interior with the cytoplasm. Until recently, these macromolecular complexes were viewed as static structures, the only function of which was to control the molecular trafficking between the two compartments. It has now become evident that this simplistic scenario is inaccurate and that nuclear pore complexes are highly dynamic multiprotein assemblies involved in diverse cellular processes ranging from the organization of the cytoskeleton to gene expression. In this review, we discuss the most recent developments in the nuclear-pore-complex field, focusing on the assembly, disassembly, maintenance and function of this macromolecular struct... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1790615 Tue, 09 Sep 2008 04:00:00 +0100 1790615 http://www.medworm.com/index.php?rid=1775847&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18774717%26dopt%3DAbstract We describe how these multiple functions selectively operate in a cellular context to control the dynamics of the actin cytoskeleton. In vivo, Spire and Cobl can synergize with other actin regulators. As an example, we outline potential methods to gain insight into the functional basis for reported genetic interactions among Spire, profilin and formin. PMID: 18774717 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1775847 Fri, 05 Sep 2008 04:00:00 +0100 1775847 http://www.medworm.com/index.php?rid=1775850&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18774293%26dopt%3DAbstract Authors: Zhou Z, Yu X In metazoan organisms, cells undergoing apoptosis are rapidly engulfed and degraded by phagocytes. Defects in apoptotic-cell clearance result in inflammatory and autoimmune responses. However, little is known about how apoptotic-cell degradation is initiated and regulated and how different phagocytic targets induce different immune responses from their phagocytes. Recent studies in mammalian systems and invertebrate model organisms have led to major progress in identifying new factors involved in the maturation of phagosomes containing apoptotic cells. These studies have delineated signaling pathways that promote the sequential incorporation of intracellular organelles to phagosomes and have also discovered that phagocytic receptors produce the signals that initia... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1775850 Thu, 04 Sep 2008 04:00:00 +0100 1775850 http://www.medworm.com/index.php?rid=1775849&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18774294%26dopt%3DAbstract Authors: Roush S, Slack FJ The first two known microRNAs (miRNAs), lin-4 and let-7, were originally discovered in the nematode Caenorhabditis elegans and control the timing of stem-cell division and differentiation. let-7 was subsequently found as the first known human miRNA. let-7 and its family members are highly conserved across species in sequence and function, and misregulation of let-7 leads to a less differentiated cellular state and the development of cell-based diseases such as cancer. Although much research has been devoted to let-7 target prediction and to understanding its biological role, research into what regulates let-7 has only just begun. Here, we review let-7-family conservation and the recent advances in understanding how let-7-expression is regulated at the transcr... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1775849 Thu, 04 Sep 2008 04:00:00 +0100 1775849 http://www.medworm.com/index.php?rid=1775848&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18774295%26dopt%3DAbstract Authors: Fan Y, Bergmann A In multi-cellular organisms, activation of apoptosis can trigger compensatory proliferation in surrounding cells to maintain tissue homeostasis. Genetic studies in Drosophila have indicated that distinct mechanisms of compensatory proliferation are employed in apoptotic tissues of different developmental states. In proliferating eye and wing tissues, the initiator caspase Dronc coordinates cell death and compensatory proliferation through the Jun N-terminal kinase and p53. The mitogens Decapentaplegic and Wingless are induced in this process. By contrast, in differentiating eye tissues, the effector caspases DrICE and Dcp-1 activate the Hedgehog signaling pathway to induce compensatory proliferation. In this review, we summarize these findings and discuss how... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1775848 Thu, 04 Sep 2008 04:00:00 +0100 1775848 http://www.medworm.com/index.php?rid=1755346&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18760924%26dopt%3DAbstract Authors: Wang H, Rudd CE Integrin adhesion is essential for aspects of immune function, including antigen presentation and migration in lymph nodes, germinal centers and sites of inflammation. Antigen receptors on B and T cells generate 'inside-out' signals for increased integrin clustering and adhesion. Although upstream components of B-cell-receptor or T-cell-receptor signaling are needed, the identity of key downstream effectors that mediate integrin adhesion is only just emerging. New candidates include immune-cell-specific adaptor proteins ADAP, SKAP-55 and SKAP-55-related (SKAP-55R). SKAP-55 has recently been identified as an effector in T cells in SKAP-55-deficient mice, whereas SKAP-55R is needed for B-cell adhesion. ADAP is required for SKAP-55 and SKAP-55R protein stability. ... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1755346 Thu, 28 Aug 2008 04:00:00 +0100 1755346 http://www.medworm.com/index.php?rid=1755347&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18760607%26dopt%3DAbstract Authors: Wood JL, Chen J The DNA-damage response (DDR) is an evolutionarily conserved signaling cascade crucial for sensing DNA damage and activating cellular responses such as cell-cycle arrest, DNA repair, senescence and apoptosis. Excitingly, two recent studies describe activation of this checkpoint in the absence of DNA damage. These studies support the idea that accumulation of checkpoint proteins and changes in global-chromatin structure are important signaling intermediates for the activation of the DDR. PMID: 18760607 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1755347 Wed, 27 Aug 2008 04:00:00 +0100 1755347 http://www.medworm.com/index.php?rid=1726649&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18715783%26dopt%3DAbstract Authors: Dansen TB, Burgering BM Members of the forkhead box O (FOXO) family of transcription factors have been postulated to be tumor suppressors because of their established roles in cell-cycle arrest, apoptosis, DNA-damage repair and scavenging of reactive oxygen species. Recently, several animal model studies have shown that the FOXO proteins are indeed tumor suppressors. Furthermore, FOXO proteins have recently been implicated in the negative regulation of signaling by the hypoxia-inducible factor 1 during vascular development, raising the possibility that the FOXO proteins suppress not only tumor formation but also tumor angiogenesis and, possibly, metastasis. Here, we discuss recent advances in the understanding of the roles of FOXO family members in tumor suppression. PMID:... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1726649 Mon, 18 Aug 2008 04:00:00 +0100 1726649 http://www.medworm.com/index.php?rid=1717700&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18706811%26dopt%3DAbstract Authors: Clarke DC, Liu X How transforming growth factor-beta (TGF-beta) signaling elicits diverse cell responses remains elusive, despite the major molecular components of the pathway being known. We contend that understanding TGF-beta biology requires mathematical models to decipher the quantitative nature of TGF-beta/Smad signaling and to account for its complexity. Here, we review mathematical models of TGF-beta superfamily signaling that predict how robustness is achieved in bone-morphogenetic-protein signaling in the Drosophila embryo, how changes in receptor-trafficking dynamics can be exploited by cancer cells and how the basic mechanisms of TGF-beta/Smad signaling conspire to promote Smad accumulation in the nucleus. These studies demonstrate the power of mathematical modeling... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1717700 Wed, 13 Aug 2008 04:00:00 +0100 1717700 http://www.medworm.com/index.php?rid=1717699&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18706812%26dopt%3DAbstract Authors: Jacobson K, Rajfur Z, Vitriol E, Hahn K Chromophore-assisted laser inactivation (CALI) is a technique whereby engineered proteins and dye molecules that produce substantial amounts of reactive oxygen species upon absorption of light are used to perturb biological systems in a spatially and temporally defined manner. CALI is an important complement to conventional genetic and pharmacological manipulations. In this review, we examine the applications of CALI to cell biology and discuss the underlying photochemical mechanisms that mediate this powerful technique. PMID: 18706812 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1717699 Wed, 13 Aug 2008 04:00:00 +0100 1717699 http://www.medworm.com/index.php?rid=1717698&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18706813%26dopt%3DAbstract Authors: Wu H, Rossi G, Brennwald P Temporal and spatial regulation of membrane-trafficking events is crucial to both membrane identity and overall cell polarity. Small GTPases of the Rab, Ral and Rho protein families have been implicated as important regulators of vesicle docking and fusion events. This review focuses on how these GTPases interact with the exocyst complex, which is a multisubunit tethering complex involved in the regulation of cell-surface transport and cell polarity. The Rab and Ral GTPases are thought to function in exocyst assembly and vesicle-tethering processes, whereas the Rho family GTPases seem to function in the local activation of the exocyst complex to facilitate downstream vesicle-fusion events. The localized activation of the exocyst by Rho GTPases is lik... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1717698 Wed, 13 Aug 2008 04:00:00 +0100 1717698 http://www.medworm.com/index.php?rid=1709864&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18703335%26dopt%3DAbstract Authors: Sherer NM, Mothes W Cells use a variety of intercellular structures, including gap junctions and synapses, for cell-cell communication. Here, we present recent advances in the understanding of thin membrane bridges that function in cell-cell signaling and intercellular transport. Cytonemes or filopodial bridges connect neighboring cells via mechanisms of adhesion, which enable ligand-receptor-mediated transfer of surface-associated cargoes from cell to cell. By contrast, tunneling nanotubes establish tubular conduits between cells that provide for the exchange of both cell-surface molecules and cytoplasmic content. We propose models for the biogenesis of both types of membrane bridges and describe how viruses use these structures for the purpose of cell-to-cell spread. PMI... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1709864 Wed, 13 Aug 2008 04:00:00 +0100 1709864 http://www.medworm.com/index.php?rid=1709865&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18701290%26dopt%3DAbstract Authors: Penzes P, Cahill ME, Jones KA, Srivastava DP Structural plasticity of excitatory synapses is a vital component of neuronal development, synaptic plasticity and behavior, and its malfunction underlies many neurodevelopmental and psychiatric disorders. However, the molecular mechanisms that control dendritic spine morphogenesis have only recently emerged. We summarize recent work that has revealed an important connection between calcium/calmodulin-dependent kinases (CaMKs) and guanine-nucleotide-exchange factors (GEFs) that activate the small GTPase Rac (RacGEFs) in controlling dendritic spine morphogenesis. These two groups of molecules function in neurons as a unique signaling cassette that transduces calcium influx into small GTPase activity and, thence, actin reorganization ... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1709865 Mon, 11 Aug 2008 04:00:00 +0100 1709865 http://www.medworm.com/index.php?rid=1664775&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18656360%26dopt%3DAbstract Authors: Peset I, Vernos I A major quest in cell biology is to understand the molecular mechanisms underlying the high plasticity of the microtubule network at different stages of the cell cycle, and during and after differentiation. Initial reports described the centrosomal localization of proteins possessing transforming acidic coiled-coil (TACC) domains. This discovery prompted several groups to examine the role of TACC proteins during cell division, leading to indications that they are important players in this complex process in different organisms. Here, we review the current understanding of the role of TACC proteins in the regulation of microtubule dynamics, and we highlight the complexity of centrosome function. PMID: 18656360 [PubMed - as supplied by publisher] (Source: T... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1664775 Wed, 23 Jul 2008 04:00:00 +0100 1664775 http://www.medworm.com/index.php?rid=1631774&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18620858%26dopt%3DAbstract Authors: Harding AS, Hancock JF Cellular signaling pathways do not simply transmit data; they integrate and process signals to operate as switches, oscillators, logic gates, memory modules and many other types of control system. These complex processing capabilities enable cells to respond appropriately to the myriad of external cues that direct growth and development. The idea that crosstalk and feedback loops are used as control systems in biological signaling networks is well established. Signaling networks are also subject to exquisite spatial regulation, yet how spatial control modulates signal outputs is less well understood. Here, we explore the spatial organization of two different signal transduction circuits: receptor tyrosine kinase activation of the mitogen-activated protei... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1631774 Thu, 10 Jul 2008 04:00:00 +0100 1631774 http://www.medworm.com/index.php?rid=1631773&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18620859%26dopt%3DAbstract Authors: Strnad P, Gönczy P The centrosome comprises a pair of centrioles and associated pericentriolar material, and it is the principal microtubule-organizing centre of most animal cells. Like the genetic material, the centrosome is duplicated once and only once during the cell cycle. Despite the fact that both doubling events are crucial for genome integrity, the understanding of the mechanisms governing centrosome duplication has lagged behind the fuller knowledge of DNA replication. Here, we review recent findings that provide important mechanistic insights into how a single procentriole forms next to each centriole once per cell cycle, thus ensuring that one centrosome becomes two. PMID: 18620859 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1631773 Thu, 10 Jul 2008 04:00:00 +0100 1631773 http://www.medworm.com/index.php?rid=1616671&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18614368%26dopt%3DAbstract Authors: Shojaei F, Zhong C, Wu X, Yu L, Ferrara N Cells of the innate immune system have a key role in maintaining homeostasis by providing the first line of defense against many pathogens. Innate immunity can also modulate the activity of acquired immunity by several mechanisms. However, subsets of myeloid cells can facilitate tumor growth, because these cells produce angiogenic factors and can also prevent the immune system from attacking tumor cells. Recent studies also emphasize the role of myeloid cells in mediating refractoriness to anti-VEGF treatments. This function of myeloid cells occurs through a proangiogenic pathway that is, at least in part, driven by the secreted protein Bv8. This review summarizes recent findings on the complex role of bone marrow-derived cells in tumo... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1616671 Mon, 07 Jul 2008 04:00:00 +0100 1616671 http://www.medworm.com/index.php?rid=1596958&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18603426%26dopt%3DAbstract Authors: Sheridan C, Martin SJ Although the molecular players are well known, the signaling thresholds that shape the decision of a cell to undergo apoptosis remain poorly understood. Using quantitative single-cell analysis approaches, a recent study has generated new insight into the molecular events that influence individual cell-death decisions. Surprisingly, this study demonstrates that cells partly committed to apoptosis can recover and also indicates, although this is as yet unproven, that such cells might harbor DNA damage that could act as a driver of oncogenesis. PMID: 18603426 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1596958 Fri, 04 Jul 2008 04:00:00 +0100 1596958 http://www.medworm.com/index.php?rid=1596957&cid=s_36137_171_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18603427%26dopt%3DAbstract Authors: Beckett K, Franch-Marro X, Vincent JP Glypicans are glycosylphosphatidylinositol-linked heparan sulfate proteoglycans that play an essential part in the regulation of morphogen signalling. Two new reports using Drosophila and mice have highlighted the importance of glypican endocytosis in the regulation of Hedgehog (Hh) signalling and in Wingless gradient formation. One Drosophila glypican, Dally-like, acts positively in Hh signalling, whereas mouse Glypican-3 is a negative regulator. This difference seems to be dependent on whether glypicans promote the internalization of Hh alone or as a complex with its receptor, Patched. PMID: 18603427 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1596957 Fri, 04 Jul 2008 04:00:00 +0100 1596957 http://www.medworm.com/index.php?rid=1561441&cid=s_36137_170_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18585040%26dopt%3DAbstract Authors: Cano A, Nieto MA Noncoding RNAs are emerging as central players in gene expression regulation through the targeting of a plethora of mRNAs. Several recent papers report on the regulation of the epithelial phenotype by the miR-200 (200 family of miRNAs) family and a natural antisense transcript, both acting on the E-cadherin repressors zinc-finger E-box-binding homeobox factors ZEB1 and ZEB2. These findings open new avenues for understanding the modulation of the epithelial-to-mesenchymal transition in physiological and pathological situations. PMID: 18585040 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1561441 Wed, 25 Jun 2008 04:00:00 +0100 1561441 http://www.medworm.com/index.php?rid=1500460&cid=s_36137_170_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18534853%26dopt%3DAbstract Authors: Fromme JC, Orci L, Schekman R Coat protein complex II (COPII) is a multi-subunit protein complex responsible for the formation of membrane vesicles at the endoplasmic reticulum. The assembly of this complex on the endoplasmic reticulum membrane needs to be tightly regulated to ensure efficient and specific incorporation of cargo proteins into nascent vesicles. Recent studies of a genetic disease affecting COPII function, and a structural analysis of COPII subunit interactions emphasize the central role of the Sec23 subunit in COPII coat assembly. Similarly, the demonstration that Sec23 interacts physically and functionally with proteins involved in both vesicle tethering and the transport along microtubules indicates that the Sec23 subunit is crucially important in linking COP... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1500460 Tue, 03 Jun 2008 04:00:00 +0100 1500460 http://www.medworm.com/index.php?rid=1497886&cid=s_36137_170_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18524595%26dopt%3DAbstract Authors: Stalder L, Mühlemann O To ensure the accuracy of gene expression, eukaryotes have evolved several surveillance mechanisms. One of the best-studied quality control mechanisms is nonsense-mediated mRNA decay (NMD), which recognizes and degrades transcripts harboring a premature translation-termination codon (PTC), thereby preventing the production of faulty proteins. NMD regulates approximately 10% of human mRNAs, and its physiological importance is manifested by the fact that approximately 30% of disease-associated mutations generate PTCs. Although different mechanisms of PTC recognition have been proposed for different species, recent studies in Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans, plants and mammals suggest a conserved model. Here, w... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1497886 Mon, 02 Jun 2008 04:00:00 +0100 1497886 http://www.medworm.com/index.php?rid=1488903&cid=s_36137_170_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18515107%26dopt%3DAbstract Authors: Sandilands E, Frame MC Endosomal trafficking is an essential cellular process involved in the transport of proteins such as integrins, hormone receptors, growth factor receptors, receptor tyrosine kinases, and lipids (e.g. sphingomyelin). Regulation of this process is highly complex and involves Arf GAPs, SNAREs, Rab proteins, Rho GTPases and the actin cytoskeleton. In this article, we focus on the intracellular targeting of the Src family of non-receptor tyrosine kinases (nRTKs), and the role of endosomes in the delivery of nRTKs to the plasma membrane. Furthermore, we discuss the role of the actin cytoskeleton in this process and consider how endosome-regulated intracellular trafficking affects cell signalling. PMID: 18515107 [PubMed - as supplied by publisher] (Source: ... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1488903 Fri, 30 May 2008 04:00:00 +0100 1488903 http://www.medworm.com/index.php?rid=1488904&cid=s_36137_170_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18514521%26dopt%3DAbstract Authors: Assoian RK, Klein EA Integrin-mediated cell attachment to the extracellular matrix is an established regulator of the cell cycle, and the best-characterized targets of this process are the cyclin D1 gene and members of the cip and kip (cip/kip) family of cdk inhibitors. Manipulation of intracellular tension affects the same targets, supporting the idea that integrin activation and intracellular tension are closely related. Several signaling cascades, including FAK, Rho GTPases and ERK, transmit the integrin and tensional signals to pathways controlling the cell cycle. However, the experimental approaches that have generated these results alter cell adhesion and tension in ways that do not reflect the subtlety of those occurring in vivo. Increasing emphasis is therefore being p... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1488904 Thu, 29 May 2008 04:00:00 +0100 1488904 http://www.medworm.com/index.php?rid=1488905&cid=s_36137_170_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18513970%26dopt%3DAbstract Authors: Gardner MK, Odde DJ, Bloom K Recent studies suggest that the human Kinesin-8 molecular motor Kif18A has a role in chromosome congression. Specifically, these studies find that Kif18A promotes chromosome congression by attenuating chromosome oscillation magnitudes. Together with recent modeling work, in vitro studies, and the analysis of in vivo yeast data, these reports reveal how Kinesin-8 molecular motors might control chromosome oscillation amplitudes by spatially regulating the dynamic instability of microtubule plus-ends within the mitotic spindle. PMID: 18513970 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1488905 Wed, 28 May 2008 04:00:00 +0100 1488905 http://www.medworm.com/index.php?rid=1478332&cid=s_36137_170_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18508269%26dopt%3DAbstract Authors: Beau I, Esclatine A, Codogno P Autophagy and the ubiquitin proteasome system (UPS) mediate the degradation of cellular proteins. However, we are now realizing that autophagy can also be a selective process that degrades various organelles. Peter and co-workers discovered a selective autophagic pathway that targets ribosomes in Saccharomyces cerevisiae. This pathway, which they termed ribophagy, depends on Ubp3 ubiquitin protease and its partner Bre5. This is an important finding, because it suggests that the number of ribosomes can be adjusted to match the needs of the cell. PMID: 18508269 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1478332 Tue, 27 May 2008 04:00:00 +0100 1478332 http://www.medworm.com/index.php?rid=1470217&cid=s_36137_170_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18502129%26dopt%3DAbstract Authors: Sabourin M, Zakian VA Telomeres, the essential structures at the ends of eukaryotic chromosomes, are composed of G-rich DNA and asociated proteins. These structures are crucial for the integrity of the genome, because they protect chromosome ends from degradation and distinguish natural ends from chromosomal breaks. The complete replication of telomeres requires a telomere-dedicated reverse transcriptase called telomerase. Paradoxically, proteins that promote the very activities against which telomeres protect, namely DNA repair, recombination and checkpoint activation, are integral to both telomeric chromatin and telomere elongation. This review focuses on recent findings that shed light on the roles of ATM-like kinases and other checkpoint and repair proteins in telomere mai... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1470217 Thu, 22 May 2008 04:00:00 +0100 1470217 http://www.medworm.com/index.php?rid=1464331&cid=s_36137_170_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18495480%26dopt%3DAbstract Authors: Kim J, Löwe T, Hoppe T The synthesis, assembly and organisation of structural and motor proteins during muscle formation requires temporal and spatial control directed by specialized chaperones. For example, alphaB-crystallin, GimC and TRiC facilitate the assembly of sarcomeric proteins such as desmin and actin. Recent studies have demonstrated that the chaperone family of UCS proteins (UNC-45-CRO1-She4p) is required for the proper function of myosin motors. Mutations in the myosin-directed chaperone unc-45, a founding member of this family, lead to disorganisation of striated muscle in Caenorhabditiselegans. In addition to the involvement of client-specific chaperones, myofibrillogenesis also involves ubiquitin-dependent degradation of regulatory muscle proteins. Here, w... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1464331 Mon, 19 May 2008 04:00:00 +0100 1464331 http://www.medworm.com/index.php?rid=1440216&cid=s_36137_170_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18468897%26dopt%3DAbstract Authors: Schumann U, Subramani S Inter-organellar communication and interactions are necessary and accepted consequences of the segregation of biochemical functions into subcellular organelles. Recently, Heidi McBride and her collaborators found a novel link between mitochondria and peroxisomes in their discovery of mitochondria-derived vesicles (MDVs), which appear to fuse with a fraction of pre-existing peroxisomes in mammalian cells. We discuss the potential role of this vesicle population in the context of pathways for the exchange of metabolites and/or macromolecules between these compartments. PMID: 18468897 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1440216 Fri, 09 May 2008 04:00:00 +0100 1440216 http://www.medworm.com/index.php?rid=1440215&cid=s_36137_170_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18472263%26dopt%3DAbstract Authors: Valenzuela-Fernández A, Cabrero JR, Serrador JM, Sánchez-Madrid F Histone deacetylase 6 (HDAC6) is a cytoplasmic enzyme that regulates many important biological processes, including cell migration, immune synapse formation, viral infection, and the degradation of misfolded proteins. HDAC6 deacetylates tubulin, Hsp90 and cortactin, and forms complexes with other partner proteins. Although HDAC6 enzymatic activity seems to be required for the regulation of cell morphology, the role of HDAC6 in lymphocyte chemotaxis is independent of its tubulin deacetylase activity. The diverse functions of HDAC6 suggest that it is a potential therapeutic target for the treatment of a range of diseases. This review examines the biological actions of HDAC6, focusing on its deacetylase a... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1440215 Thu, 08 May 2008 04:00:00 +0100 1440215 http://www.medworm.com/index.php?rid=1440219&cid=s_36137_170_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18468438%26dopt%3DAbstract This article reviews recent studies that have provided evidence for new mechanisms of clock organization and function. These mechanisms include protein-protein interactions and the regulation of protein stability, which, together, directly connect light signalling to the Arabidopsis circadian system. Evidence of rhythmic changes in chromatin structure has also opened new and exciting ways for regulation of clock gene expression. All of these mechanisms ensure an appropriate synchronization with the environment, which is crucial for successful plant growth and development. PMID: 18468438 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology) Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1440219 Wed, 07 May 2008 04:00:00 +0100 1440219 http://www.medworm.com/index.php?rid=1440218&cid=s_36137_170_f&fid=36137&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18468439%26dopt%3DAbstract Authors: Lev S, Halevy DB, Peretti D, Dahan N The VAMP-associated proteins (VAPs) are highly conserved integral endoplasmic reticulum membrane proteins implicated in diverse cellular functions, including the regulation of lipid transport and homeostasis, membrane trafficking, neurotransmitter release, stabilization of presynaptic microtubules, and the unfolded protein response. Recently, a single missense mutation within the human VAP-B gene was identified in three forms of familial motor neuron disease. In this review, we integrate results from studies of yeast, fly and mammalian VAPs that provide insight into the structural features of these proteins, the network of VAP-interacting proteins, their possible physiological functions, and their involvement in motor neuron disease. PM... Trends in Cell Biology journals http://www.medworm.com/rss/comments.php?id=1440218 Wed, 07 May 2008 04:00:00 +0100 1440218