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The reggie/flotillin connection to growth.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 dynami...
Source: Trends in Cell Biology - November 5, 2009 Category: Cytology Authors: Stuermer CA Tags: Trends Cell Biol Source Type: journals

Polycomb group complexes - many combinations, many functions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 b...
Source: Trends in Cell Biology - November 2, 2009 Category: Cytology Authors: Kerppola TK Tags: Trends Cell Biol Source Type: journals

Transcription-independent p53 apoptosis: an alternative route to death.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 rol...
Source: Trends in Cell Biology - October 29, 2009 Category: Cytology Authors: Speidel D Tags: Trends Cell Biol Source Type: journals

Dynamic chromosome movements during meiosis: a way to eliminate unwanted connections?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Trends in Cell Biology - October 22, 2009 Category: Cytology Authors: Koszul R, Kleckner N Tags: Trends Cell Biol Source Type: journals

Oxidation of potassium channels by ROS: a general mechanism of aging and neurodegeneration?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Trends in Cell Biology - October 20, 2009 Category: Cytology Authors: Sesti F, Liu S, Cai SQ Tags: Trends Cell Biol Source Type: journals

Nuclear phosphoinositides: a signaling enigma wrapped in a compartmental conundrum.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 f...
Source: Trends in Cell Biology - October 18, 2009 Category: Cytology Authors: Barlow CA, Laishram RS, Anderson RA Tags: Trends Cell Biol Source Type: journals

Photoactivatable fluorescent proteins for diffraction-limited and super-resolution imaging.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ce...
Source: Trends in Cell Biology - October 14, 2009 Category: Cytology Authors: Lippincott-Schwartz J, Patterson GH Tags: Trends Cell Biol Source Type: journals

Imaging endocytic clathrin structures in living cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 app...
Source: Trends in Cell Biology - October 14, 2009 Category: Cytology Authors: Kirchhausen T Tags: Trends Cell Biol Source Type: journals

Cellular quiescence: are controlling genes conserved?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 supe...
Source: Trends in Cell Biology - October 12, 2009 Category: Cytology Authors: Yanagida M Tags: Trends Cell Biol Source Type: journals

The future's bright: Imaging cell biology in the 21st century.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19833517 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology)
Source: Trends in Cell Biology - October 12, 2009 Category: Cytology Authors: Hosking CR, Schwartz JL Tags: Trends Cell Biol Source Type: journals

Open source bioimage informatics for cell biology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 th...
Source: Trends in Cell Biology - October 12, 2009 Category: Cytology Authors: Swedlow JR, Eliceiri KW Tags: Trends Cell Biol Source Type: journals

A single molecule view of gene expression.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 i...
Source: Trends in Cell Biology - October 7, 2009 Category: Cytology Authors: Larson DR, Singer RH, Zenklusen D Tags: Trends Cell Biol Source Type: journals

DNA repair: easy to visualize, difficult to elucidate.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 DN...
Source: Trends in Cell Biology - October 7, 2009 Category: Cytology Authors: Nagy Z, Soutoglou E Tags: Trends Cell Biol Source Type: journals

Shining new light on 3D cell motility and the metastatic process.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 diagnost...
Source: Trends in Cell Biology - October 7, 2009 Category: Cytology Authors: Provenzano PP, Eliceiri KW, Keely PJ Tags: Trends Cell Biol Source Type: journals

Fluorescent proteins: a cell biologist's user guide.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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-fus...
Source: Trends in Cell Biology - October 7, 2009 Category: Cytology Authors: Snapp EL Tags: Trends Cell Biol Source Type: journals

Green light to illuminate signal transduction events.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 fl...
Source: Trends in Cell Biology - October 6, 2009 Category: Cytology Authors: Balla T Tags: Trends Cell Biol Source Type: journals

Partial internal reflections on total internal reflection fluorescent microscopy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Trends in Cell Biology - October 6, 2009 Category: Cytology Authors: Simon SM Tags: Trends Cell Biol Source Type: journals

Soft X-ray tomography and cryogenic light microscopy: the cool combination in cellular imaging.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 function...
Source: Trends in Cell Biology - October 6, 2009 Category: Cytology Authors: McDermott G, Le Gros MA, Knoechel CG, Uchida M, Larabell CA Tags: Trends Cell Biol Source Type: journals

Phosphoinositides, exocytosis and polarity in yeast: all about actin?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Trends in Cell Biology - October 6, 2009 Category: Cytology Authors: Yakir-Tamang L, Gerst JE Tags: Trends Cell Biol Source Type: journals

Caught in the act: quantifying protein behaviour in living cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 b...
Source: Trends in Cell Biology - October 1, 2009 Category: Cytology Authors: Lidke DS, Wilson BS Tags: Trends Cell Biol Source Type: journals

Control of neuronal polarity and plasticity - a renaissance for microtubules?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 remarkabl...
Source: Trends in Cell Biology - October 1, 2009 Category: Cytology Authors: Hoogenraad CC, Bradke F Tags: Trends Cell Biol Source Type: journals

PolyQ fibrillation in the cell nucleus: who's bad?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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-protea...
Source: Trends in Cell Biology - September 28, 2009 Category: Cytology Authors: von Mikecz A Tags: Trends Cell Biol Source Type: journals

The Kindlin protein family: new members to the club of focal adhesion proteins.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ex...
Source: Trends in Cell Biology - September 16, 2009 Category: Cytology Authors: Meves A, Stremmel C, Gottschalk K, Fässler R Tags: Trends Cell Biol Source Type: journals

Crosstalk in Met receptor oncogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Trends in Cell Biology - September 13, 2009 Category: Cytology Authors: Lai AZ, Abella JV, Park M Tags: Trends Cell Biol Source Type: journals

Plasmodesmata - bridging the gap between neighboring plant cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Trends in Cell Biology - September 9, 2009 Category: Cytology Authors: Lucas WJ, Ham BK, Kim JY Tags: Trends Cell Biol Source Type: journals

Mitotic phosphatases: from entry guards to exit guides.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Trends in Cell Biology - September 3, 2009 Category: Cytology Authors: Bollen M, Gerlich DW, Lesage B Tags: Trends Cell Biol Source Type: journals

Cytokinetic abscission: cellular dynamics at the midbody.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 assemb...
Source: Trends in Cell Biology - September 1, 2009 Category: Cytology Authors: Steigemann P, Gerlich DW Tags: Trends Cell Biol Source Type: journals

Molecular mediators of macrophage fusion.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 fusi...
Source: Trends in Cell Biology - September 1, 2009 Category: Cytology Authors: Helming L, Gordon S Tags: Trends Cell Biol Source Type: journals

Chemotaxis: finding the way forward with Dictyostelium.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 intra...
Source: Trends in Cell Biology - September 1, 2009 Category: Cytology Authors: King JS, Insall RH Tags: Trends Cell Biol Source Type: journals

The regulation of aging: does autophagy underlie longevity?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 lif...
Source: Trends in Cell Biology - August 30, 2009 Category: Cytology Authors: Vellai T, Takács-Vellai K, Sass M, Klionsky DJ Tags: Trends Cell Biol Source Type: journals

To localize or not to localize: mRNA fate is in 3'UTR ends.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Trends in Cell Biology - August 25, 2009 Category: Cytology Authors: Andreassi C, Riccio A Tags: Trends Cell Biol Source Type: journals

Molecular mechanisms involved in inflammasome activation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 interleuki...
Source: Trends in Cell Biology - August 25, 2009 Category: Cytology Authors: Bryant C, Fitzgerald KA Tags: Trends Cell Biol Source Type: journals

Multi-level molecular clutches in motile cell processes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, a...
Source: Trends in Cell Biology - August 25, 2009 Category: Cytology Authors: Giannone G, Mège RM, Thoumine O Tags: Trends Cell Biol Source Type: journals

Microtubule-dependent cell morphogenesis in the fission yeast.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 pol...
Source: Trends in Cell Biology - August 24, 2009 Category: Cytology Authors: Martin SG Tags: Trends Cell Biol Source Type: journals

Tetraspanin-enriched microdomains: a functional unit in cell plasma membranes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 compartment...
Source: Trends in Cell Biology - August 23, 2009 Category: Cytology Authors: Yáñez-Mó M, Barreiro O, Gordon-Alonso M, Sala-Valdés M, Sánchez-Madrid F Tags: Trends Cell Biol Source Type: journals

Do membrane undulations help cells probe the world?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 later...
Source: Trends in Cell Biology - August 23, 2009 Category: Cytology Authors: Pierres A, Monnet-Corti V, Benoliel AM, Bongrand P Tags: Trends Cell Biol Source Type: journals

Intracellular transport by active diffusion.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Trends in Cell Biology - August 19, 2009 Category: Cytology Authors: Brangwynne CP, Koenderink GH, Mackintosh FC, Weitz DA Tags: Trends Cell Biol Source Type: journals

Scaffolds: interaction platforms for cellular signalling circuits.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Trends in Cell Biology - July 31, 2009 Category: Cytology Authors: Zeke A, Lukács M, Lim WA, Reményi A Tags: Trends Cell Biol Source Type: journals

New regulatory mechanisms of TGF-beta receptor function.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 regul...
Source: Trends in Cell Biology - July 30, 2009 Category: Cytology Authors: Kang JS, Liu C, Derynck R Tags: Trends Cell Biol Source Type: journals

The NF-kappaB-independent functions of IKK subunits in immunity and cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 cance...
Source: Trends in Cell Biology - July 30, 2009 Category: Cytology Authors: Chariot A Tags: Trends Cell Biol Source Type: journals

Novel ubiquitin-dependent quality control in the endoplasmic reticulum.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Trends in Cell Biology - July 21, 2009 Category: Cytology Authors: Feldman M, Gisou van der Goot F Tags: Trends Cell Biol Source Type: journals

The spliceosome: a self-organized macromolecular machine in the nucleus?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 clu...
Source: Trends in Cell Biology - July 16, 2009 Category: Cytology Authors: Rino J, Carmo-Fonseca M Tags: Trends Cell Biol Source Type: journals

Neurofibroma development in NF1 - insights into tumour initiation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Trends in Cell Biology - July 14, 2009 Category: Cytology Authors: Parrinello S, Lloyd AC Tags: Trends Cell Biol Source Type: journals

G-quadruplex structures: in vivo evidence and function.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 r...
Source: Trends in Cell Biology - July 6, 2009 Category: Cytology Authors: Lipps HJ, Rhodes D Tags: Trends Cell Biol Source Type: journals

Regulation of centrosome separation in yeast and vertebrates: Common threads.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Trends in Cell Biology - June 30, 2009 Category: Cytology Authors: Lim HH, Zhang T, Surana U Tags: Trends Cell Biol Source Type: journals

Centrosome function in cancer: guilty or innocent?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Trends in Cell Biology - June 28, 2009 Category: Cytology Authors: Zyss D, Gergely F Tags: Trends Cell Biol Source Type: journals

Intraflagellar transport and the generation of dynamic, structurally and functionally diverse cilia.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ce...
Source: Trends in Cell Biology - June 24, 2009 Category: Cytology Authors: Silverman MA, Leroux MR Tags: Trends Cell Biol Source Type: journals

A quest for the mechanism regulating global planar cell polarity of tissues.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 controll...
Source: Trends in Cell Biology - June 24, 2009 Category: Cytology Authors: Wu J, Mlodzik M Tags: Trends Cell Biol Source Type: journals

Roles of endosomal trafficking in neurite outgrowth and guidance.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Trends in Cell Biology - June 16, 2009 Category: Cytology Authors: Sann S, Wang Z, Brown H, Jin Y Tags: Trends Cell Biol Source Type: journals

Emerging roles for myosin II and cytoplasmic dynein in migrating neurons and growth cones.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 pub...
Source: Trends in Cell Biology - June 10, 2009 Category: Cytology Authors: Vallee RB, Seale GE, Tsai JW Tags: Trends Cell Biol Source Type: journals