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372 records returned

The replication fork's five degrees of freedom, their failure and genome rearrangements.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genome rearrangements are important in pathology and evolution. The thesis of this review is that the genome is in peril when replication forks stall, and stalled forks are normally rescued by error-free mechanisms. Failure of error-free mechanisms results in large-scale chromosome changes called gross chromosomal rearrangements, GCRs, by the aficionados. In this review we discuss five error-free mechanisms a replication fork may use to overcome blockage, mechanisms that are still poorly understood. We then speculate on how genome rearrangements may occur when such mechanisms fail. Replication fork recovery failure may...
Source: Current Opinion in Cell Biology - November 11, 2009 Category: Cytology Authors: Weinert T, Kaochar S, Jones H, Paek A, Clark A Tags: Curr Opin Cell Biol Source Type: journals

Life and death decisions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19896817 [PubMed - as supplied by publisher] (Source: Current Opinion in Cell Biology)
Source: Current Opinion in Cell Biology - November 5, 2009 Category: Cytology Authors: Amon A, Tyers M Tags: Curr Opin Cell Biol Source Type: journals

Conservation and divergence in developmental networks: a view from Drosophila myogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Understanding developmental networks has recently been enhanced through the identification of a large number of conserved essential regulators. Interspecies comparisons of the transcriptional networks regulated by these factors are still at a rather early stage, with limited global data available. Here we use the accumulating phenotypic information from multiple species to provide initial insights into the wiring and rewiring of developmental networks, with particular emphasis on myogenesis, a highly conserved developmental process. This review highlights the most recent findings on the transcriptional program driving ...
Source: Current Opinion in Cell Biology - November 4, 2009 Category: Cytology Authors: Ciglar L, Furlong EE Tags: Curr Opin Cell Biol Source Type: journals

Rautenlippe Redux-toward a unified view of the precerebellar rhombic lip.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The rhombic lip (aka rautenlippe) is a germinative neuroepithelium rimming the opening of the hindbrain fourth ventricle during development. Studies spanning more than a century have shown that the rhombic lip produces numerous brainstem neuronal populations unique in their development and functions. While these studies have largely been anatomical in nature, recent applications of newer techniques such as genetic fate mapping and conditional mutagenesis have resolved the rhombic lip into numerous molecularly distinct progenitor domains along spatial and temporal axes that give rise to specific neuron subtypes and syst...
Source: Current Opinion in Cell Biology - October 31, 2009 Category: Cytology Authors: Ray RS, Dymecki SM Tags: Curr Opin Cell Biol Source Type: journals

A fresh breeze from the ivory tower.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19880301 [PubMed - as supplied by publisher] (Source: Current Opinion in Cell Biology)
Source: Current Opinion in Cell Biology - October 30, 2009 Category: Cytology Authors: Birchmeier C Tags: Curr Opin Cell Biol Source Type: journals

Glucose metabolism and programmed cell death: an evolutionary and mechanistic perspective.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We examined the metabolic foundations of apoptosis from a Darwinian context and suggest that PCD has evolved from the cellular response to metabolic stress, most notably in relation to glucose metabolism. Whilst apoptosis and other forms of PCD are essential to the development, maintenance and survival of multicellular organisms, it is now evident that controlled and selective cell death confers fitness advantages in unicellular organisms. All species may thus harbour a fundamental relationship between the availability of basic nutrients and life/death decisions. This evolutionary perspective may inform our understanding o...
Source: Current Opinion in Cell Biology - October 20, 2009 Category: Cytology Authors: King A, Gottlieb E Tags: Curr Opin Cell Biol Source Type: journals

Regulation of cell death by the ubiquitin-proteasome system.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The regulation of apoptosis (programmed cell death) has been the subject of a vast body of research because of its implications in normal development, tissue homeostasis and a wide range of diseases. The ubiquitin-proteasome system (UPS) plays a prominent role in the control of apoptosis by targeting key cell death proteins, including caspases, the central executioners of apoptosis. Here we summarize the major findings on the function of the UPS in both pro- and anti-apoptotic regulation. PMID: 19850458 [PubMed - as supplied by publisher] (Source: Current Opinion in Cell Biology)
Source: Current Opinion in Cell Biology - October 20, 2009 Category: Cytology Authors: Bader M, Steller H Tags: Curr Opin Cell Biol Source Type: journals

Sister chromatid tension and the spindle assembly checkpoint.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The spindle assembly checkpoint (SAC) is a feedback control system that monitors the state of kinetochore/microtubule attachment during mitosis and halts cell cycle progression until all chromosomes are properly aligned at the metaphase plate. The state of chromosome-microtubule attachment is implicated as a crucial factor in the checkpoint response. On the contrary, lack of tension in the centromere-kinetochore region of sister chromatids has been shown to regulate a pathway of correction of undesired chromosome-microtubule connections, while the presence of tension is believed to promote the stabilization of attachme...
Source: Current Opinion in Cell Biology - October 18, 2009 Category: Cytology Authors: Nezi L, Musacchio A Tags: Curr Opin Cell Biol Source Type: journals

Herding Hippos: regulating growth in flies and man.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Control of cell number requires the coordinate regulation of cell proliferation and cell death. Studies in both the fly and mouse have identified the Hippo kinase pathway as a key signaling pathway that controls cell proliferation and apoptosis. Several studies have implicated the Hippo pathway in a variety of cancers. Recent studies have also revealed a role for the Hippo pathway in the control of cell fate decisions during development. In this review, we will cover the current model of Hippo signaling in development. We will explore the differences between the Hippo pathway in invertebrates and mammals, and focus on ...
Source: Current Opinion in Cell Biology - October 18, 2009 Category: Cytology Authors: Badouel C, Garg A, McNeill H Tags: Curr Opin Cell Biol Source Type: journals

Making the Auroras glow: regulation of Aurora A and B kinase function by interacting proteins.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The conserved Aurora family of protein kinases have emerged as crucial regulators of mitosis and cytokinesis. Despite their high degree of homology, Aurora A and B have very distinctive localisations and functions: Aurora A associates with the spindle poles to regulate entry into mitosis, centrosome maturation and spindle assembly; Aurora B is a member of the Chromosomal Passenger Complex (CPC) that transfers from the inner centromere in early mitosis to the spindle midzone, equatorial cortex and midbody in late mitosis and cytokinesis. Aurora B functions include regulation of chromosome-microtubule interactions, cohes...
Source: Current Opinion in Cell Biology - October 14, 2009 Category: Cytology Authors: Carmena M, Ruchaud S, Earnshaw WC Tags: Curr Opin Cell Biol Source Type: journals

Myc's other life: stem cells and beyond.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Over the last three decades genetic and biochemical studies have revealed the pleiotropic effects of the Myc oncoprotein. While cell line studies have defined the intracellular processes regulated by Myc such as proliferation, differentiation, and metabolic growth, in vivo studies have confirmed these functions, and revealed roles in acquisition and maintenance of stem cell properties. These roles may be partially mediated by Myc's capacity to modify the chromatin landscape on a global scale. Myc also regulates numerous protein-coding transcripts, and many noncoding RNAs (rRNAs, tRNAs, and miRNAs). As Myc activity dire...
Source: Current Opinion in Cell Biology - October 13, 2009 Category: Cytology Authors: Laurenti E, Wilson A, Trumpp A Tags: Curr Opin Cell Biol Source Type: journals

Mitochondrial cell death effectors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe how BCL-2-family members preserve or disrupt mitochondrial integrity, the contribution of BH3-only proteins to this process, and the importance of cytotoxic factors released by the mitochondria. The growing evidence that the intrinsic pathway is crucial for tumourigenesis makes this an intriguing field. In particular, the finding that BCL-2 homologues are inhibited by BH3-only proteins may have future therapeutic applications. PMID: 19822411 [PubMed - as supplied by publisher] (Source: Current Opinion in Cell Biology)
Source: Current Opinion in Cell Biology - October 9, 2009 Category: Cytology Authors: Brenner D, Mak TW Tags: Curr Opin Cell Biol Source Type: journals

Quantitative proteomics: a tool to assess cell differentiation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
During cell differentiation, gene expression is regulated at multiple levels which is only partially captured by transcription profiling. In recent years it became increasingly clear that post-translational modifications of core histones and post-transcriptional regulation by RNA-binding proteins and microRNAs play an important role during differentiation. Recent advances in mass spectrometry-based quantitative proteomics now allow for genome-wide analyses at the protein level. This technology provides a powerful toolbox that can be used to study different levels of gene regulation and reveal their importance during de...
Source: Current Opinion in Cell Biology - September 30, 2009 Category: Cytology Authors: Vermeulen M, Selbach M Tags: Curr Opin Cell Biol Source Type: journals

Growth control and ribosome biogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Ribosomes provide the basis for protein production and this drives cell growth. Recent studies, both in yeast and in higher eukaryotes, are beginning to reveal new mechanisms underlying the elaborate control of ribosome biogenesis, which requires coordinate regulation of all three RNA polymerases. Transcription of ribosomal RNA is finely tuned to cellular energy status and linked to the production of ribosomal proteins. Several autoregulatory mechanisms controlling various aspects of ribosome biogenesis have been uncovered and reveal new connections to cell-cycle and cell-size control. Ribosome biogenesis has now been ...
Source: Current Opinion in Cell Biology - September 28, 2009 Category: Cytology Authors: Lempiäinen H, Shore D Tags: Curr Opin Cell Biol Source Type: journals

Mitochondrial reactive oxygen species regulate hypoxic signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Physiological hypoxia results in a host of responses that include increased ventilation, constriction of the pulmonary artery, and a cellular transcriptional program that promotes glycolysis, angiogenesis, and erythropoiesis. Mitochondria are the primary consumers of cellular oxygen and have thus been speculated for years to be the site of cellular oxygen sensing. Many of the cellular responses to hypoxia are now known to be mediated by the production of reactive oxygen species at mitochondrial complex III. While the mechanism by which cytosolic oxidant concentration is increased during hypoxia is unknown, the importan...
Source: Current Opinion in Cell Biology - September 22, 2009 Category: Cytology Authors: Hamanaka RB, Chandel NS Tags: Curr Opin Cell Biol Source Type: journals

Cellular and nuclear degradation during apoptosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Apoptosis ensures quick death and quiet clearance of unwanted or damaged cells, without inducing much, if any, immunological responses from the organism. In metazoan organisms, apoptotic cells are swiftly engulfed by other cells. The degradation of cellular content is initiated in apoptotic cells and completed within engulfing cells. In apoptotic cells, caspase-mediated proteolysis cleaves protein substrates into fragments; nuclear DNA is partially degraded into nucleosomal units; and autophagy potentially contributes to apoptotic cell removal. In engulfing cells, specific signaling pathways promote the sequential fusi...
Source: Current Opinion in Cell Biology - September 22, 2009 Category: Cytology Authors: He B, Lu N, Zhou Z Tags: Curr Opin Cell Biol Source Type: journals

How to make beta cells?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Insulin-producing beta cells are lost or insufficient in diabetic patients, presenting the medical challenge for new beta cells. Currently, there are three strategies that offer promise. One involves the generation of beta cells de novo by directing the differentiation of either embryonic stem cells or induced pluripotent cells to the beta cell lineage. The second is based on the conversion of another terminally differentiated cell to beta cells in a process called reprogramming. The third approach is to promote the replication of existing beta cells either in vivo or in vitro. Significant progress is evident for each ...
Source: Current Opinion in Cell Biology - September 22, 2009 Category: Cytology Authors: Borowiak M, Melton DA Tags: Curr Opin Cell Biol Source Type: journals

Dynamic regulation of Notch signaling in neural progenitor cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In the developing nervous system, differentiating neurons express Delta and activate Notch signaling in their neighboring cells. As a result of Notch activation, neuronal differentiation is inhibited in neighboring cells and they remain neural progenitor cells. Thus, differentiation of neurons and maintenance of neural progenitor cells are well balanced owing to Notch signaling. Recent studies revealed that Notch signaling is under the control of more complex and dynamic regulation than previously thought, such as cell cycle dependent activation and oscillating gene expression. We discuss here recent advances in unders...
Source: Current Opinion in Cell Biology - September 21, 2009 Category: Cytology Authors: Kageyama R, Ohtsuka T, Shimojo H, Imayoshi I Tags: Curr Opin Cell Biol Source Type: journals

Control of cell growth by the SCF and APC/C ubiquitin ligases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The ubiquitin-proteasome system plays key roles in the control of cell growth. The cell cycle, in particular, is highly regulated by the functions of the SCF and APC/C ubiquitin ligases, and perturbation of their function can result in tumorigenesis. Although the SCF and APC/C complexes are well established in growth control pathways, many aspects of their function remain unknown. Recent studies have shed light on the mechanism of SCF-mediated ubiquitination and new functions for the SCF complex and APC/C. Our expanding understanding of the roles of the SCF and APC/C complexes highlight the potential for targeted molec...
Source: Current Opinion in Cell Biology - September 20, 2009 Category: Cytology Authors: Skaar JR, Pagano M Tags: Curr Opin Cell Biol Source Type: journals

Cell-to-cell contact and extracellular matrix.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19773151 [PubMed - as supplied by publisher] (Source: Current Opinion in Cell Biology)
Source: Current Opinion in Cell Biology - September 18, 2009 Category: Cytology Authors: Humphries MJ, Reynolds A Tags: Curr Opin Cell Biol Source Type: journals

Protein phosphatases take the mitotic stage.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Following the identification of cyclin-dependent kinases in the 1980s, kinases were hailed as the directors of mitosis. Although the action of kinases must necessarily be reversible, only recently has the involvement of specific phosphatases in mitosis become appreciated. Studies are now revealing how the timely execution of mitotic events depends on the delicate interplay between kinases and phosphatases. To date, the best-characterized mitotic phosphatases are Cdc25, that is required for entry into mitosis and Cdc14, that controls exit from mitosis in budding yeast. Recent work has now exposed the conserved serine-th...
Source: Current Opinion in Cell Biology - September 17, 2009 Category: Cytology Authors: De Wulf P, Montani F, Visintin R Tags: Curr Opin Cell Biol Source Type: journals

TOR signaling in invertebrates.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Target of Rapamycin (TOR), a protein kinase, is the central node of a highly conserved signaling network that regulates cell growth in response to nutrients, hormones, and stresses. TOR is found in two functionally distinct complexes, TORC1 and TORC2. In this review we address the most recent advances in TOR signaling in invertebrate model organisms, including yeasts, plants, worms, and insects. PMID: 19767189 [PubMed - as supplied by publisher] (Source: Current Opinion in Cell Biology)
Source: Current Opinion in Cell Biology - September 17, 2009 Category: Cytology Authors: Soulard A, Cohen A, Hall MN Tags: Curr Opin Cell Biol Source Type: journals

Eukaryotic DNA replication control: Lock and load, then fire.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The initiation of chromosomal DNA replication involves initiator proteins that recruit and load hexameric DNA helicases at replication origins. This helicase loading step is tightly regulated in bacteria and eukaryotes. In contrast to the situation in bacteria, the eukaryotic helicase is loaded in an inactive form. This extra 'lock and load' mechanism in eukaryotes allows regulation of a second step, helicase activation. The temporal separation of helicase loading and activation is crucial for the coordination of DNA replication with cell growth and extracellular signals, the prevention of re-replication and the contro...
Source: Current Opinion in Cell Biology - September 17, 2009 Category: Cytology Authors: Remus D, Diffley JF Tags: Curr Opin Cell Biol Source Type: journals

Cytoskeletal control of growth and cell fate switching.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Living cells must be able to switch between growth and differentiation with high fidelity and precise spatial control to ensure that normal tissue patterns are formed in the embryo and maintained throughout adult life. Most work on cell proliferation focuses on elucidating the signaling pathways responsible for control of cell cycle progression that are triggered by cell binding to soluble growth factors and insoluble extracellular matrix. Here we review recent work, which has revealed that mechanical tension-dependent changes in cell shape and cytoskeletal structure are equally critical for control of growth, as well ...
Source: Current Opinion in Cell Biology - September 6, 2009 Category: Cytology Authors: Mammoto A, Ingber DE Tags: Curr Opin Cell Biol Source Type: journals

Polarity proteins regulate mammalian cell-cell junctions and cancer pathogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The epithelial cells of multicellular organisms form highly organized tissues specialized for the tasks of protection, secretion, and absorption, all of which require tight regulation of the core processes of cell polarity and tissue architecture. Disruption of these core processes is a critical feature of epithelial tumors. Cell polarity and tissue architecture are intimately linked, as proteins controlling cell shape are also responsible for proper localization and assembly of cell-cell junctions and three-dimensional tissue organization. The extracellular matrix underlying epithelial tissues supports tissue architec...
Source: Current Opinion in Cell Biology - August 31, 2009 Category: Cytology Authors: Feigin ME, Muthuswamy SK Tags: Curr Opin Cell Biol Source Type: journals

The skinny on Fat: an enormous cadherin that regulates cell adhesion, tissue growth, and planar cell polarity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Fat is an extremely large atypical cadherin involved in the regulation of cell adhesion, tissue growth, and planar cell polarity (PCP). Recent studies have begun to illuminate the mechanisms by which Fat performs these functions during development. Fat relays signals to the Hippo pathway to regulate tissue growth, and to PCP proteins to regulate tissue patterning. In this review we briefly cover the historical data demonstrating that Fat regulates tissue growth and tissue patterning, and then focus on advances in the past three years illuminating the mechanisms by which Fat controls growth and planar polarity in flies ...
Source: Current Opinion in Cell Biology - August 10, 2009 Category: Cytology Authors: Sopko R, McNeill H Tags: Curr Opin Cell Biol Source Type: journals

Plakophilins: multifunctional scaffolds for adhesion and signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Armadillo family proteins known as plakophilins have been characterized as structural components of desmosomes that stabilize and strengthen adhesion by enhancing attachments with the intermediate filament cytoskeleton. However, plakophilins and their close relatives are emerging as versatile scaffolds for multiple signaling and metabolic processes that not only facilitate junction dynamics but also more globally regulate diverse cellular activities. While perturbation of plakophilin functions contribute to inherited diseases and cancer pathogenesis, the functional significance of the multiple PKP isoforms and the mech...
Source: Current Opinion in Cell Biology - August 9, 2009 Category: Cytology Authors: Bass-Zubek AE, Godsel LM, Delmar M, Green KJ Tags: Curr Opin Cell Biol Source Type: journals

Matrix metalloproteinase proteomics: substrates, targets, and therapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Proteomics encompasses powerful techniques termed 'degradomics' for unbiased high-throughput protease substrate discovery screens that have been applied to an important family of extracellular proteases, the matrix metalloproteinases (MMPs). Together with the data generated from genetic deletion and transgenic mouse models and genomic profiling, these screens can uncover the diverse range of MMP functions, reveal which MMPs and MMP-mediated pathways exacerbate pathology, and which are involved in protection and the resolution of disease. This information can be used to identify and validate candidate drug targets and a...
Source: Current Opinion in Cell Biology - July 15, 2009 Category: Cytology Authors: Morrison CJ, Butler GS, Rodríguez D, Overall CM Tags: Curr Opin Cell Biol Source Type: journals

Control of cell adhesion dynamics by Rap1 signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Individual cells in their particular environments adhere to the extracellular matrix (ECM) and their neighbours via integrin-containing and cadherin-containing complexes, respectively. The dynamics of these interactions regulate the formation and maintenance of complex tissues. An expanding body of evidence accentuates the role of the small Rap1 GTPase and its associated signaling network in many of these processes. In this review we will discuss more recently revealed roles of Rap1 signaling by primarily focusing on functions of the Rap1 effectors RIAM, KRIT-1/CCM1 and AF-6/Afadin in junctional regulation of the vascu...
Source: Current Opinion in Cell Biology - July 14, 2009 Category: Cytology Authors: Boettner B, Van Aelst L Tags: Curr Opin Cell Biol Source Type: journals

Stem cells, microenvironment mechanics, and growth factor activation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Physicochemical features of a cell's microenvironment can exert important effects on cell behavior and include the effects of matrix elasticity on cell differentiation processes, but molecular mechanisms are largely mysterious. Here we highlight recent reports of a mechanical dependence to growth factor activation, with a particular focus on release of TGFbeta (Transforming Growth Factor beta) from its large latent complex via forced unfolding. We discuss these processes and pathways in the contexts of matrix adhesion and fluid shearing as they might relate to stem cell differentiation and other mechanisms in developme...
Source: Current Opinion in Cell Biology - July 14, 2009 Category: Cytology Authors: Tenney RM, Discher DE Tags: Curr Opin Cell Biol Source Type: journals

Structural determinants of Junctional Adhesion Molecule A (JAM-A) function and mechanisms of intracellular signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Junctional Adhesion Molecule A (JAM-A) is a multifunctional cell surface protein that has multiple evolutionarily conserved structural features. There is now conclusive evidence that discrete structural elements on JAM-A mediate intracellular signaling events that alter cell migration and paracellular permeability. Specifically, self-dimerization between extracellular Ig-like loops and close apposition of PDZ-dependent, JAM-A-associated intracellular scaffold proteins such as Afadin and guanine-nucleotide exchange factors mediate activation of Rap1 and modulation of epithelial cell migration by effects on beta1 integri...
Source: Current Opinion in Cell Biology - July 13, 2009 Category: Cytology Authors: Severson EA, Parkos CA Tags: Curr Opin Cell Biol Source Type: journals

Vps-C complexes: gatekeepers of endolysosomal traffic.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genetic studies in yeast, plants, insects, and mammals have identified four universally conserved proteins, together called Vps Class C, that are essential for late endosome and lysosome assembly and for numerous endolysosomal trafficking pathways, including the terminal stages of autophagy. Two Vps-C complexes, HOPS and CORVET, incorporate diverse biochemical functions: they tether membranes, stimulate Rab nucleotide exchange, guide SNARE assembly to drive membrane fusion, and possibly act as ubiquitin ligases. Recent studies offer new insight into the complex relationships between Vps-C complexes and their cognate Ra...
Source: Current Opinion in Cell Biology - July 2, 2009 Category: Cytology Authors: Nickerson DP, Brett CL, Merz AJ Tags: Curr Opin Cell Biol Source Type: journals

How adhesion signals reach a mitochondrial conclusion-ECM regulation of apoptosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A fundamental aspect in metazoans is the ability of a cell to recognise its positional context within a tissue. This is important in both development and homeostasis, where cell proliferation, differentiation and apoptosis are strictly controlled to form and maintain tissues. Much information has been generated on how cells receive and interpret adhesion-mediated signals. The non-receptor tyrosine kinase, Fak (focal adhesion kinase) has received much attention with regard to adhesion mediated signalling, including its role in survival. Survival signals are required to suppress the default pathway of apoptosis. The ulti...
Source: Current Opinion in Cell Biology - June 28, 2009 Category: Cytology Authors: Gilmore AP, Owens TW, Foster FM, Lindsay J Tags: Curr Opin Cell Biol Source Type: journals

Cell biology of the ESCRT machinery.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The ESCRT (endosomal sorting complex required for transport) machinery comprises a set of protein complexes that regulate sorting and trafficking into multivesicular bodies en route to the lysosome. The physical mechanism responsible for generating lumenal vesicles in this pathway is unknown. Here we review recent studies suggesting that components of the ESCRT-III complex drive lumenal vesicle formation and consider possible mechanisms for this reaction. PMID: 19560911 [PubMed - as supplied by publisher] (Source: Current Opinion in Cell Biology)
Source: Current Opinion in Cell Biology - June 25, 2009 Category: Cytology Authors: Hanson PI, Shim S, Merrill SA Tags: Curr Opin Cell Biol Source Type: journals

How ILK and kindlins cooperate to orchestrate integrin signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Integrin-mediated cell adhesion regulates multiple cellular processes crucial for development, physiology, and pathology. Since integrins lack enzymatic activity they need to recruit adaptor and signaling proteins to mediate their functions. The cytoplasmic proteins kindlins and integrin-linked kinase (ILK) associate with integrin tails and thereby link integrins with the actin cytoskeleton and various signaling pathways. In comparison to their role in regulating integrin function in cell-matrix adhesions, less is known about the functions of kindlins and ILK in other cellular compartments, such as cell-cell contacts a...
Source: Current Opinion in Cell Biology - June 24, 2009 Category: Cytology Authors: Böttcher RT, Lange A, Fässler R Tags: Curr Opin Cell Biol Source Type: journals

Membranes and organelles.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19559586 [PubMed - as supplied by publisher] (Source: Current Opinion in Cell Biology)
Source: Current Opinion in Cell Biology - June 23, 2009 Category: Cytology Authors: Odorizzi G, Rehling P Tags: Curr Opin Cell Biol Source Type: journals

Adhesion within the stem cell niches.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Growing body of evidence confirms that cell-cell and cell-extracellular matrix adhesion within stem cell niches is essential for the establishment and maintenance of niche architecture, for the generation and transmission of short-distance regulatory signals, and for controlling the frequency and nature of stem cell divisions. Recent studies demonstrated that in many stem cell niches, adhesion to support cells and/or extracellular matrix determines orientation of stem cell division plane, thereby contributing to the control of stem cell self-renewal and differentiation. Thus, although further analysis of the implicated...
Source: Current Opinion in Cell Biology - June 14, 2009 Category: Cytology Authors: Raymond K, Deugnier MA, Faraldo MM, Glukhova MA Tags: Curr Opin Cell Biol Source Type: journals

The signaling mechanisms of syndecan heparan sulfate proteoglycans.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Syndecans are membrane proteins controlling cell proliferation, differentiation, adhesion, and migration. Their extracellular domains bear versatile heparan sulfate chains that provide structural determinants for syndecans to function as coreceptors or activators for molecules like growth factors and constituents of the matrix. Syndecans also signal via their protein cores and their conserved transmembrane and cytoplasmic domains. The direct interactions and signaling cascades they support are becoming better characterized. These interactions are regulated by phosphorylation, induced clustering and shedding of the synd...
Source: Current Opinion in Cell Biology - June 14, 2009 Category: Cytology Authors: Lambaerts K, Wilcox-Adelman SA, Zimmermann P Tags: Curr Opin Cell Biol Source Type: journals

Extracellular microfibrils: contextual platforms for TGFbeta and BMP signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The extracellular matrix plays a key role in organ formation and tissue homeostasis. Recent studies have revealed that fibrillin assemblies (microfibrils) confer both tissue integrity and regulate signaling events that instruct cell performance and that perturbation of either function manifests in disease. These analyses have also indicated that fibrillin assemblies impart contextual specificity to TGFbeta and BMP signaling. Moreover, correlative evidence suggests functional coupling between cell-directed assembly of microfibrils and targeting of TGFbeta and BMP complexes to fibrillins. Hence, the emerging view is that...
Source: Current Opinion in Cell Biology - June 11, 2009 Category: Cytology Authors: Ramirez F, Rifkin DB Tags: Curr Opin Cell Biol Source Type: journals

Focal adhesion kinase: switching between GAPs and GEFs in the regulation of cell motility.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Focal adhesion (FA) kinase (FAK) is a cytoplasmic protein-tyrosine kinase involved in cytoskeleton remodeling, formation and disassembly of cell adhesion structures, and in the regulation of Rho-family GTPases. Therefore, FAK is widely accepted as an important promoter of directional cell movement. Recent studies have elucidated new molecular connections of FAK in these processes. Specifically, FAK facilitates the localized and cyclic activation of guanine nucleotide exchange factors (GEFs) and GTPases-activating proteins (GAPs). In general, GEFs activate, while GAPs inactivate RhoGTPases. Therefore, FAK is in a unique...
Source: Current Opinion in Cell Biology - June 11, 2009 Category: Cytology Authors: Tomar A, Schlaepfer DD Tags: Curr Opin Cell Biol Source Type: journals

Mechanical modes of 'amoeboid' cell migration.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The morphological term 'amoeboid' migration subsumes a number of rather distinct biophysical modes of cellular locomotion that range from blebbing motility to entirely actin-polymerization-based gliding. Here, we discuss the diverse principles of force generation and force transduction that lead to the distinct amoeboid phenotypes. We argue that shifting the balance between actin protrusion, actomyosin contraction, and adhesion to the extracellular substrate can explain the different modes of amoeboid movement and that blebbing and gliding are barely extreme variants of one common migration strategy. Depending on the c...
Source: Current Opinion in Cell Biology - June 10, 2009 Category: Cytology Authors: Lämmermann T, Sixt M Tags: Curr Opin Cell Biol Source Type: journals

Nuclear pore complex biogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Nuclear pore complexes (NPCs) are the sole mediators of transport between the nucleus and the cytoplasm. NPCs have a life cycle: they assemble, disassemble, turnover, and age. The molecular mechanisms governing these different vital steps are beginning to emerge, suggesting key roles for the core structural scaffold of the NPC and auxiliary factors in the assembly of this large macromolecular complex, and connections between NPC maintenance, NPC turnover, and aging of the cell. PMID: 19524430 [PubMed - as supplied by publisher] (Source: Current Opinion in Cell Biology)
Source: Current Opinion in Cell Biology - June 10, 2009 Category: Cytology Authors: Fernandez-Martinez J, Rout MP Tags: Curr Opin Cell Biol Source Type: journals

Turnover of organelles by autophagy in yeast.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Efficient detection and removal of superfluous or damaged organelles are crucial to maintain cellular homeostasis and to assure cell survival. Growing evidence shows that organelles or parts of them can be removed by selective subtypes of otherwise unselective macroautophagy and microautophagy. This requires both the adaptation of the core autophagic machinery and sophisticated mechanisms to recognize organelles destined for turnover. We review the current knowledge on autophagic removal of peroxisomes, mitochondria, ER and parts of the nucleus with an emphasis on yeasts as a model eukaryote. PMID: 19515549 [PubMed...
Source: Current Opinion in Cell Biology - June 7, 2009 Category: Cytology Authors: Farré JC, Krick R, Subramani S, Thumm M Tags: Curr Opin Cell Biol Source Type: journals

AP-3-dependent trafficking and disease: the first decade.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The adaptor protein (AP)-3 complex defines a pathway for the intracellular trafficking of membrane-associated proteins in most eukaryotic cells. Ten years ago, genetic defects in AP-3 were linked to a human Mendelian disease, named Hermansky-Pudlak syndrome, characterized by abnormal biogenesis and function of lysosome-related organelles such as melanosomes and platelet dense granules. During recent years, research on this trafficking pathway has significantly expanded its horizons to include evolutionarily divergent eukaryotic models and to embrace functional genomics and proteomics approaches. These studies have brou...
Source: Current Opinion in Cell Biology - June 1, 2009 Category: Cytology Authors: Dell'angelica EC Tags: Curr Opin Cell Biol Source Type: journals

Execution of nonsense-mediated mRNA decay: what defines a substrate?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The nonsense-mediated mRNA decay (NMD) pathway targets mRNAs with premature termination codons as well as a subset of normal mRNAs for rapid decay. Emerging evidence suggests that mRNAs become NMD substrates based on the composition of the mRNP downstream of the translation termination event, which either stimulates or antagonizes recruitment of the NMD machinery. The NMD mRNP subsequently undergoes several remodeling events, which involve hydrolysis of ATP by the NMD factor Upf1 and in metazoans, a phosphorylation/dephosphorylation cycle of Upf1 mediated by Smg proteins. This leads to mRNA decay following translationa...
Source: Current Opinion in Cell Biology - May 31, 2009 Category: Cytology Authors: Rebbapragada I, Lykke-Andersen J Tags: Curr Opin Cell Biol Source Type: journals

Replisome structure and conformational dynamics underlie fork progression past obstacles.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Replisomes are multiprotein complexes that unzip the parental helix and duplicate the separated strands during genome replication. The antiparallel structure of DNA poses unique geometric constraints to the process, and the replisome has evolved unique dynamic features that solve this problem. Interestingly, the solution to duplex DNA replication has been co-opted to solve many other important problems that replisomes must contend with during the duplication of long chromosomes. For example, along its path the replisome will encounter lesions and DNA-bound proteins. Recent studies show that the replisome can circumvent...
Source: Current Opinion in Cell Biology - May 31, 2009 Category: Cytology Authors: Yao NY, O'Donnell M Tags: Curr Opin Cell Biol Source Type: journals

Polysomes, P bodies and stress granules: states and fates of eukaryotic mRNAs.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The control of translation and mRNA degradation plays a key role in the regulation of eukaryotic gene expression. In the cytosol, mRNAs engaged in translation are distributed throughout the cytosol, while translationally inactive mRNAs can accumulate in P bodies, in complex with mRNA degradation and translation repression machinery, or in stress granules, which appear to be mRNAs stalled in translation initiation. Here we discuss how these different granules suggest a dynamic model for the metabolism of cytoplasmic mRNAs wherein they cycle between different mRNP states with different functional properties and subcellul...
Source: Current Opinion in Cell Biology - May 31, 2009 Category: Cytology Authors: Balagopal V, Parker R Tags: Curr Opin Cell Biol Source Type: journals

The basal initiation machinery: beyond the general transcription factors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In vitro experiments led to a simple model in which basal transcription factors sequentially assembled with RNA Polymerase II to generate a preinitiation complex (PIC). Emerging evidence indicates that PIC composition is not universal, but promoter-dependent. Active promoters are occupied by a mixed population of complexes, including regulatory factors such as NC2, Mot1, Mediator, and TFIIS. Recent studies are expanding our understanding of the roles of these factors, demonstrating that their functions are both broader and more context dependent than previously realized. PMID: 19411170 [PubMed - in process] (Source...
Source: Current Opinion in Cell Biology - May 31, 2009 Category: Cytology Authors: Sikorski TW, Buratowski S Tags: Curr Opin Cell Biol Source Type: journals

MicroRNAs and cancer--new paradigms in molecular oncology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The 'classic' view of molecular oncology indicates that cancer is a genetic disease involving tumor suppressor and oncogenic proteins. However, in the recent years, it has been demonstrated that small regulatory non-coding RNAs (ncRNAs) named microRNAs (miRNAs) are involved in human tumorigenesis, thus revealing a new layer in the molecular architecture of human cancer. Gene expression studies revealed that hundreds of miRNAs are deregulated in cancer cells and functional studies clarified that miRNAs are involved in all the molecular and biological processes that drive tumorigenesis. Here, we summarize the recent adva...
Source: Current Opinion in Cell Biology - May 31, 2009 Category: Cytology Authors: Negrini M, Nicoloso MS, Calin GA Tags: Curr Opin Cell Biol Source Type: journals

Nucleus and gene expression.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19447016 [PubMed - in process] (Source: Current Opinion in Cell Biology)
Source: Current Opinion in Cell Biology - May 31, 2009 Category: Cytology Authors: Izaurralde E, Zamore PD Tags: Curr Opin Cell Biol Source Type: journals