Hot off the presses! Dec 01 trends cell biol

The Dec 01 issue of the trends cell biol is now up on Pubget (About trends cell biol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Editorial Board
  - trends cell biol 20(12):i (2010)
  
• CellBio-X: celebrating the interface between Cell Biology and other disciplines
  - trends cell biol 20(12):689-690 (2010)
  
• Finding the key – cell biology and science education
  - trends cell biol 20(12):691-694 (2010)
  No international research community, cell biology included, can exist without an educational community to renew and replenish it. Unfortunately, cell biology researchers frequently regard their work as independent of the process of education and see little reason to reach out to science teachers. For cell biology to continue to prosper, I argue that researchers must support education in at least three ways. First, we must view education and research as part of a single scientific community. Second, we should take advantage of new technologies to connect the research laboratory to the classroom. Finally, we must take the initiative in defending the integrity of science teaching, particularly when education is under attack for political or religious reasons.
• Unconventional allies: interdisciplinary approaches to science policy and funding
  - trends cell biol 20(12):695-698 (2010)
  Scientific research is an often misunderstood, undervalued and yet essential activity. Many nonscientists think that research is quick and easy, and that science is a compilation of established facts rather than rigorous conclusions based on available evidence. In addition, many nonscientists, and perhaps many scientists as well, forget that our social and financial investment is small relative to the massive and expensive problems that we all want scientific research to solve. Using biomedical research in the United States as an example, I will argue that countering this underinvestment in science will require broadening perspectives in the scientific community as well as coupling expanded individual advocacy and education efforts to an interdisciplinary advocacy approach. This approach is in many ways analogous to the unique solutions that emerge when scientists working in different disciplines leave their intellectual silos and work together.
• Animating the model figure
  - trends cell biol 20(12):699-704 (2010)
  In all branches of scientific inquiry, researchers build models that enable them to visualize, formulate and communicate their hypotheses to others. In cell biology, our conceptual understanding of a process is typically embodied in a model figure. These visual models should ideally represent pre-existing knowledge of molecular interactions, movement, structure and localization but, in reality, they often fall short. Cell biologists have begun to look to the use of three-dimensional animation to visualize and describe complex molecular and cellular events. In addition to aiding teaching and communication, animation is emerging as a powerful tool for providing researchers with insight into the processes that they study. Two case studies focusing on the structure/function of the motor protein dynein and the structure of the centriole are discussed.
• Engineered materials and the cellular microenvironment: a strengthening interface between cell biology and bioengineering
  - trends cell biol 20(12):705-714 (2010)
  Cells constantly probe and respond to a myriad of cues that are present in their local surroundings. The effects of soluble cues are relatively straightforward to manipulate, yet teasing apart how cells transduce signals from the extracellular matrix and neighboring cells has proven to be challenging due to the spatially and mechanically complex adhesive interactions. Over the years, advances in the engineering of biocompatible materials have enabled innovative ways to study adhesion-mediated cell functions, and numerous insights have elucidated the significance of the cellular microenvironment. Here, we highlight some of the major approaches and discuss the potential for future advancement.
• Stem cell-based biological tooth repair and regeneration
  - trends cell biol 20(12):715-722 (2010)
  Teeth exhibit limited repair in response to damage, and dental pulp stem cells probably provide a source of cells to replace those damaged and to facilitate repair. Stem cells in other parts of the tooth, such as the periodontal ligament and growing roots, play more dynamic roles in tooth function and development. Dental stem cells can be obtained with ease, making them an attractive source of autologous stem cells for use in restoring vital pulp tissue removed because of infection, in regeneration of periodontal ligament lost in periodontal disease, and for generation of complete or partial tooth structures to form biological implants. As dental stem cells share properties with mesenchymal stem cells, there is also considerable interest in their wider potential to treat disorders involving mesenchymal (or indeed non-mesenchymal) cell derivatives, such as in Parkinson's disease.
• Transcription by the numbers redux: experiments and calculations that surprise
  - trends cell biol 20(12):723-733 (2010)
  The study of transcription has witnessed an explosion of quantitative effort both experimentally and theoretically. In this article we highlight some of the exciting recent experimental efforts in the study of transcription with an eye to the demands that such experiments put on theoretical models of transcription. From a modeling perspective, we focus on two broad classes of models: the so-called thermodynamic models that use statistical mechanics to reckon the level of gene expression as probabilities of promoter occupancy, and rate-equation treatments that focus on the temporal evolution of the activity of a given promoter and that make it possible to compute the distributions of messenger RNA and proteins. We consider several appealing case studies to illustrate how quantitative models have been used to dissect transcriptional regulation.
• Diverse evolutionary paths to cell adhesion
  - trends cell biol 20(12):734-742 (2010)
  The morphological diversity of animals, fungi, plants, and other multicellular organisms stems from the fact that each lineage acquired multicellularity independently. A prerequisite for each origin of multicellularity was the evolution of mechanisms for stable cell-cell adhesion or attachment. Recent advances in comparative genomics and phylogenetics provide critical insights into the evolutionary foundations of cell adhesion. Reconstructing the evolution of cell junction proteins in animals and their unicellular relatives exemplifies the roles of co-option and innovation. Comparative studies of volvocine algae reveal specific molecular changes that accompanied the evolution of multicellularity in Volvox. Comparisons between animals and Dictyostelium show how commonalities and differences in the biology of unicellular ancestors influenced the evolution of adhesive mechanisms. Understanding the unicellular ancestry of cell adhesion helps illuminate the basic cell biolo! gy of multicellular development in modern organisms.

Hot off the presses! Sep 01 Trends Cell Biol

The Sep 01 issue of the Trends Cell Biol is now up on Pubget (About Trends Cell Biol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Contents page + Editorial Board
  - Trends Cell Biol 21(9):i (2011)
  
• Productive tension: force-sensing and homeostasis of cell–cell junctions
  - Trends Cell Biol 21(9):499-505 (2011)
  Cell–cell contacts are major determinants of tissue organization in both health and disease. Adhesive interactions, especially those mediated by classical cadherin receptors, influence cell–cell recognition and tissue patterning during development. Conversely, cadherin dysfunction promotes tumor progression to invasion and metastasis. Over the past three decades, we have learnt a great deal about the molecular mechanisms responsible for cadherin-based cell–cell interactions. Yet our knowledge remains incomplete. The intersection between cell biology and mechanical forces has long been suspected to be an important missing factor in understanding cadherin biology. However, tangible evidence remained elusive until recently, when several reports began to elucidate the role of cadherins and the cytoskeleton in mechanotransduction. In this review, we examine these advances and discuss their implications.
• The SecY complex: conducting the orchestra of protein translocation
  - Trends Cell Biol 21(9):506-514 (2011)
  Like the conductor of an orchestra, the Sec protein translocation channel is the platform needed to bring together the many different players required for the constitutive and obligatory process of protein transport. This conserved membrane channel, termed SecY in bacteria and Sec61 in eukaryotes, creates a ubiquitous protein-conducting pathway by which thousands of newly synthesized polypeptides make their way through the lipid bilayer. The channel is not a simple passive pore, however; it displays remarkable complexity by interacting with numerous soluble partners, including SecA, Syd, FtsY and the ribosome in bacteria. For several decades, scientists have been fascinated by the sophistication and versatility of this transport channel. In this review, we cover the current state of the field including some of the newest and most exciting findings on channel structure and mechanism of action.
• Membrane-trafficking sorting hubs: cooperation between PI4P and small GTPases at the trans-Golgi network
  - Trends Cell Biol 21(9):515-525 (2011)
  Cell polarity in eukaryotes requires constant sorting, packaging and transport of membrane-bound cargo within the cell. These processes occur in two sorting hubs: the recycling endosome for incoming material and the trans-Golgi network for outgoing material. Phosphatidylinositol 3-phosphate and phosphatidylinositol 4-phosphate are enriched at the endocytic and exocytic sorting hubs, respectively, where they act together with small GTPases to recruit factors to segregate cargo and regulate carrier formation and transport. In this review, we summarize the current understanding of how these lipids and GTPases regulate membrane trafficking directly, emphasizing the recent discoveries of phosphatidylinositol 4-phosphate functions at the trans-Golgi network.
• Fly meets yeast: checking the correct orientation of cell division
  - Trends Cell Biol 21(9):526-533 (2011)
  Cell division is generally thought to be a process that produces an exact copy of the mother cell by precisely replicating its genomic DNA, doubling organelles, and segregating them into two cells. Many cell types from bacteria to human cells divide asymmetrically, however, to generate daughter cells with distinct characteristics. Such asymmetric divisions are fundamental to the lifespan of a cell, to embryonic development, and to stem cell homeostasis. Asymmetric division requires coordination of cellular asymmetry and the cell division machinery. Accumulating evidence suggests that the basic molecular mechanisms that govern this process are conserved from yeast to humans. In this review we highlight similarities in the mechanisms of asymmetric cell division in yeast and Drosophila male germline stem cells (GSCs) in the hope of extracting common themes underlying several systems.
• Histone ADP-ribosylation in DNA repair, replication and transcription
  - Trends Cell Biol 21(9):534-542 (2011)
  Most published work on post-translational histone modifications focuses on small covalent alterations such as acetylation, methylation and phosphorylation. By contrast, fewer data are available on the modification of histones by ADP-ribose. Discussion of the biological significance of histone ADP-ribosylation has often been restricted to functions of the modifying enzymes, rather than to histones as ADP-ribose acceptors. In particular, the identification of specific lysine residues as ADP-ribose acceptor sites in histones and the identification of ADP-ribose binding modules raise this modification to a par with acetylation, methylation or phosphorylation. We discuss here the functional aspects of histone ADP-ribosylation and its influence on DNA repair, replication and transcription.
• Biological hydrogels as selective diffusion barriers
  - Trends Cell Biol 21(9):543-551 (2011)
  The controlled exchange of molecules between organelles, cells, or organisms and their environment is crucial for life. Biological gels such as mucus, the extracellular matrix (ECM), and the biopolymer barrier within the nuclear pore are well suited to achieve such a selective exchange, allowing passage of particular molecules while rejecting many others. Although hydrogel-based filters are integral parts of biology, clear concepts of how their barrier function is controlled at a microscopic level are still missing. We summarize here our current understanding of how selective filtering is established by different biopolymer-based hydrogels. We ask if the modulation of microscopic particle transport in biological hydrogels is based on a generic filtering principle which employs biochemical/biophysical interactions with the filtered molecules rather than size-exclusion effects.
• Deciphering condensin action during chromosome segregation
  - Trends Cell Biol 21(9):552-559 (2011)
  The correct segregation of eukaryotic genomes requires the resolution of sister DNA molecules and their movement into opposite halves of the cell before cell division. The dynamic changes chromosomes need to undergo during these events depend on the action of a multi-subunit SMC (structural maintenance of chromosomes) protein complex named condensin, but its molecular function in chromosome segregation is still poorly understood. Recent studies suggest that condensin has a role in the removal of sister chromatid cohesin, in sister chromatid decatenation by topoisomerases, and in the structural reconfiguration of mitotic chromosomes. In this review we discuss possible mechanisms that could explain the variety of condensin actions during chromosome segregation.

Hot off the presses! Aug 01 Trends Cell Biol

The Aug 01 issue of the Trends Cell Biol is now up on Pubget (About Trends Cell Biol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Editorial Board
  - Trends Cell Biol 21(8):i (2011)
  
• pRB, a tumor suppressor with a stabilizing presence
  - Trends Cell Biol 21(8):433-441 (2011)
  The product of the retinoblastoma tumor-susceptibility gene (RB1) is a key regulator of cell proliferation and this function is thought to be central to its tumor suppressive activity. Several studies have demonstrated that inactivation of pRB not only allows inappropriate proliferation but also undermines mitotic fidelity, leading to genome instability and ploidy changes. Such properties promote tumor evolution and correlate with increased resistance to therapeutics and tumor relapse. These observations suggest that inactivation of pRB could contribute to both tumor initiation and progression. Further characterization of the role of pRB in chromosome segregation will provide insight into processes that are misregulated in human tumors and could reveal new therapeutic targets to kill or stall these chromosomally unstable lesions. We review the evidence that pRB promotes genome stability and discuss the mechanisms that probably contribute to this effect.
• Reconstructing regulatory network transitions
  - Trends Cell Biol 21(8):442-451 (2011)
  Cellular responses often involve a transition of cells from one state to another. A transition from a stem cell to a differentiated cell state, for example, might occur in response to gene expression changes induced by a transcription factor, or to signaling cascades triggered by a hormone or pathogen. Regulatory networks are thought to control such cellular transitions. Thus, many researchers are interested in reconstructing regulatory networks, not only with the aim of gaining a deeper understanding of cellular transitions, but also of using networks to predict and potentially manipulate cellular transitions and outcomes. In this review, we highlight approaches to the reconstruction of regulatory networks underlying cellular transitions, with special attention to transcriptional regulatory networks. We describe recent regulatory network reconstructions in a variety of organisms, and discuss the success they share in identifying new regulatory components, shared relat! ionships and phenotypic outcomes.
• Coupling mitosis to DNA replication: The emerging role of the histone H4-lysine 20 methyltransferase PR-Set7
  - Trends Cell Biol 21(8):452-460 (2011)
  To ensure accurate inheritance of genetic information through cell proliferation, chromosomes must be precisely copied only during S phase, and then correctly condensed and segregated during mitosis. Several new findings suggest that this tight coupling between DNA replication and mitosis is in part controlled by cell cycle regulated chromatin modifications, in particular due to the changing activity of lysine methyltransferase PR-Set7/SET8 that is responsible for the monomethylation of histone H4 at lysine 20. Cell cycle oscillation of PR-Set7 is orchestrated by ubiquitin-mediated proteolysis, and interference with this regulatory process leads to unscheduled licensing of replication origins and altered timing of mitotic chromosome compaction. This review provides an overview of how PR-Set7 regulates these two cell cycle events and highlights questions that remain to be addressed.
• Atomic force microscopy: a nanoscopic window on the cell surface
  - Trends Cell Biol 21(8):461-469 (2011)
  Atomic force microscopy (AFM) techniques provide a versatile platform for imaging and manipulating living cells to single-molecule resolution, thereby enabling us to address pertinent questions in key areas of cell biology, including cell adhesion and signalling, embryonic and tissue development, cell division and shape, and microbial pathogenesis. In this review, we describe the principles of AFM, and survey recent breakthroughs made in AFM-based cell nanoscopy, showing how the technology has increased our molecular understanding of the organization, mechanics, interactions and processes of the cell surface. We also discuss the advantages and limitations of AFM techniques, and the challenges remaining to be addressed in future research.
• Cdk5rap2 exposes the centrosomal root of microcephaly syndromes
  - Trends Cell Biol 21(8):470-480 (2011)
  Autosomal recessive primary microcephaly (MCPH) is characterized by small brain size as a result of deficient neuron production in the developing cerebral cortex. Although MCPH is a rare disease, the questions surrounding its etiology strike at the core of stem cell biology. The seven genes implicated in MCPH all encode centrosomal proteins and disruption of the MCPH gene Cdk5rap2 in mice revealed its role in neural progenitor proliferation and in maintaining normal centriole replication control. We discuss here the impact that centrosome regulation has upon neural progenitors in the developing brain. We integrate the impact of centriole replication defects with the functions of Cdk5rap2 and other MCPH proteins, propose mechanisms for progenitor loss in MCPH, and discuss links to two other microcephaly syndromes.
• Unraveling the enigma: progress towards understanding the coronin family of actin regulators
  - Trends Cell Biol 21(8):481-488 (2011)
  Coronins are a conserved family of actin cytoskeleton regulators that promote cell motility and modulate other actin-dependent processes. Although these proteins have been known for 20 years, substantial progress has been made in the past 5 years towards their understanding. In this review, we examine this progress, place it into the context of what was already known, and pose several questions that remain to be addressed. In particular, we cover the emerging consensus about the role of Type I coronins in coordinating the function of Arp2/3 complex and ADF/cofilin proteins. This coordination plays an important role in leading-edge actin dynamics and overall cell motility. Finally, we discuss the roles played by the more exotic coronins of the Type II and III classes in cellular processes away from the leading edge.
• Microfluidic devices for studying chemotaxis and electrotaxis
  - Trends Cell Biol 21(8):489-497 (2011)
  Directed cell migration plays important roles in physiological processes such as host defense, wound healing, cancer metastasis and embryogenesis. Many organisms are capable of directional migration, which can be guided by diverse cellular factors including chemical and electrical cues. Recently, microfluidic devices that consist of small channels with micrometer dimensions are being developed for cell migration studies. These devices can precisely configure and flexibly manipulate chemical concentration gradients and electric fields, and thus can be used to study the complex guiding mechanisms for cell migration. In this paper we highlight recent applications of microfluidic devices for cell migration research, with a focus on electric field-directed cell migration, to provide important and timely updates of this rapidly developing research field.

Hot off the presses! Aug 01 Trends Cell Biol

The Aug 01 issue of the Trends Cell Biol is now up on Pubget (About Trends Cell Biol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Editorial Board
  - Trends Cell Biol 21(8):i (2011)
  
• pRB, a tumor suppressor with a stabilizing presence
  - Trends Cell Biol 21(8):433-441 (2011)
  The product of the retinoblastoma tumor-susceptibility gene (RB1) is a key regulator of cell proliferation and this function is thought to be central to its tumor suppressive activity. Several studies have demonstrated that inactivation of pRB not only allows inappropriate proliferation but also undermines mitotic fidelity, leading to genome instability and ploidy changes. Such properties promote tumor evolution and correlate with increased resistance to therapeutics and tumor relapse. These observations suggest that inactivation of pRB could contribute to both tumor initiation and progression. Further characterization of the role of pRB in chromosome segregation will provide insight into processes that are misregulated in human tumors and could reveal new therapeutic targets to kill or stall these chromosomally unstable lesions. We review the evidence that pRB promotes genome stability and discuss the mechanisms that probably contribute to this effect.
• Reconstructing regulatory network transitions
  - Trends Cell Biol 21(8):442-451 (2011)
  Cellular responses often involve a transition of cells from one state to another. A transition from a stem cell to a differentiated cell state, for example, might occur in response to gene expression changes induced by a transcription factor, or to signaling cascades triggered by a hormone or pathogen. Regulatory networks are thought to control such cellular transitions. Thus, many researchers are interested in reconstructing regulatory networks, not only with the aim of gaining a deeper understanding of cellular transitions, but also of using networks to predict and potentially manipulate cellular transitions and outcomes. In this review, we highlight approaches to the reconstruction of regulatory networks underlying cellular transitions, with special attention to transcriptional regulatory networks. We describe recent regulatory network reconstructions in a variety of organisms, and discuss the success they share in identifying new regulatory components, shared relat! ionships and phenotypic outcomes.
• Coupling mitosis to DNA replication: The emerging role of the histone H4-lysine 20 methyltransferase PR-Set7
  - Trends Cell Biol 21(8):452-460 (2011)
  To ensure accurate inheritance of genetic information through cell proliferation, chromosomes must be precisely copied only during S phase, and then correctly condensed and segregated during mitosis. Several new findings suggest that this tight coupling between DNA replication and mitosis is in part controlled by cell cycle regulated chromatin modifications, in particular due to the changing activity of lysine methyltransferase PR-Set7/SET8 that is responsible for the monomethylation of histone H4 at lysine 20. Cell cycle oscillation of PR-Set7 is orchestrated by ubiquitin-mediated proteolysis, and interference with this regulatory process leads to unscheduled licensing of replication origins and altered timing of mitotic chromosome compaction. This review provides an overview of how PR-Set7 regulates these two cell cycle events and highlights questions that remain to be addressed.
• Atomic force microscopy: a nanoscopic window on the cell surface
  - Trends Cell Biol 21(8):461-469 (2011)
  Atomic force microscopy (AFM) techniques provide a versatile platform for imaging and manipulating living cells to single-molecule resolution, thereby enabling us to address pertinent questions in key areas of cell biology, including cell adhesion and signalling, embryonic and tissue development, cell division and shape, and microbial pathogenesis. In this review, we describe the principles of AFM, and survey recent breakthroughs made in AFM-based cell nanoscopy, showing how the technology has increased our molecular understanding of the organization, mechanics, interactions and processes of the cell surface. We also discuss the advantages and limitations of AFM techniques, and the challenges remaining to be addressed in future research.
• Cdk5rap2 exposes the centrosomal root of microcephaly syndromes
  - Trends Cell Biol 21(8):470-480 (2011)
  Autosomal recessive primary microcephaly (MCPH) is characterized by small brain size as a result of deficient neuron production in the developing cerebral cortex. Although MCPH is a rare disease, the questions surrounding its etiology strike at the core of stem cell biology. The seven genes implicated in MCPH all encode centrosomal proteins and disruption of the MCPH gene Cdk5rap2 in mice revealed its role in neural progenitor proliferation and in maintaining normal centriole replication control. We discuss here the impact that centrosome regulation has upon neural progenitors in the developing brain. We integrate the impact of centriole replication defects with the functions of Cdk5rap2 and other MCPH proteins, propose mechanisms for progenitor loss in MCPH, and discuss links to two other microcephaly syndromes.
• Unraveling the enigma: progress towards understanding the coronin family of actin regulators
  - Trends Cell Biol 21(8):481-488 (2011)
  Coronins are a conserved family of actin cytoskeleton regulators that promote cell motility and modulate other actin-dependent processes. Although these proteins have been known for 20 years, substantial progress has been made in the past 5 years towards their understanding. In this review, we examine this progress, place it into the context of what was already known, and pose several questions that remain to be addressed. In particular, we cover the emerging consensus about the role of Type I coronins in coordinating the function of Arp2/3 complex and ADF/cofilin proteins. This coordination plays an important role in leading-edge actin dynamics and overall cell motility. Finally, we discuss the roles played by the more exotic coronins of the Type II and III classes in cellular processes away from the leading edge.
• Microfluidic devices for studying chemotaxis and electrotaxis
  - Trends Cell Biol 21(8):489-497 (2011)
  Directed cell migration plays important roles in physiological processes such as host defense, wound healing, cancer metastasis and embryogenesis. Many organisms are capable of directional migration, which can be guided by diverse cellular factors including chemical and electrical cues. Recently, microfluidic devices that consist of small channels with micrometer dimensions are being developed for cell migration studies. These devices can precisely configure and flexibly manipulate chemical concentration gradients and electric fields, and thus can be used to study the complex guiding mechanisms for cell migration. In this paper we highlight recent applications of microfluidic devices for cell migration research, with a focus on electric field-directed cell migration, to provide important and timely updates of this rapidly developing research field.

Hot off the presses! Apr 01 trends cell biol

The Apr 01 issue of the trends cell biol is now up on Pubget (About trends cell biol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Editorial Board
  - trends cell biol 21(4):i (2011)
  
• The Three Musketeers of Autophagy: phosphorylation, ubiquitylation and acetylation
  - trends cell biol 21(4):195-201 (2011)
  Autophagy is a highly conserved process that allows cells, tissues and organs to survive onslaughts such as nutrient deprivation, inflammation, hypoxia and other stresses. The core component proteins that regulate autophagy are well known, and the formation of a double-membrane structure that encompasses cytosolic cargo, including protein aggregates and organelles, has been intensively studied. However, less is known about the inputs that specifically alter recruitment of these components and how post-translational modifications can influence autophagy flux, or the rate at which autophagy substrates are turned over. We propose that three types of post-translational modifications – phosphorylation, ubiquitylation and acetylation – are crucial for autophagy induction, regulation and fine-tuning, and are influenced by a variety of stimuli. Understanding these novel mechanisms of autophagy regulation will give us deeper insights into this process and potentially open u! p therapeutic avenues.
• Evolutionary origins of STIM1 and STIM2 within ancient Ca2+ signaling systems
  - trends cell biol 21(4):202-211 (2011)
  Human stromal interaction molecule (STIM) proteins are parts of elaborate eukaryotic Ca2+ signaling systems that include numerous plasma membrane (PM), endoplasmic reticulum (ER), and mitochondrial Ca2+ transporters, channels and regulators. STIM2 and STIM1 function as Ca2+ sensors with different sensitivities for ER Ca2+. They translocate to ER–PM junctions and open PM Orai Ca2+ influx channels when receptor-mediated Ca2+ release lowers ER Ca2+ levels. The resulting increase in cytosolic Ca2+ leads to the activation of numerous Ca2+ effector proteins that in turn regulate differentiation, cell contraction, secretion and other cell functions. In this review, we use an evolutionary perspective to survey molecular activation mechanisms in the Ca2+ signaling system, with a particular focus on regulatory motifs and functions of the two STIM proteins. We discuss the presence and absence of STIM genes in different species, the order of appearance of STIM versus Orai, and t! he evolutionary addition of new signaling domains to STIM proteins.
• Regeneration in plants and animals: dedifferentiation, transdifferentiation, or just differentiation?
  - trends cell biol 21(4):212-218 (2011)
  The textbooks and literature of plant biology indicate that plant cells are totipotent, and that regeneration occurs via dedifferentiation, by which the cell and its descendents recapitulate earlier stages of development. However, recent work on the generation of callus, a presumed undifferentiated or dedifferentiated and disorganized cellular mass, indicates that the cells of callus are neither, and that callus forms predominantly from a pre-existing population of stem cells. Recent work in animal regeneration, for example in salamander limbs, also indicates that previous assumptions about the extent of dedifferentiation and pluripotency in animals are in need of critical reassessment. We review here some of these data, compare plant and animal regeneration, and argue that the importance of dedifferentiation and plasticity in regenerating systems is due for reevaluation.
• The endoplasmic reticulum and protein trafficking in dendrites and axons
  - trends cell biol 21(4):219-227 (2011)
  Neurons are highly polarized cells whose dendrites and axons extend long distances from the cell body to form synapses that mediate neuronal communication. The trafficking of membrane lipids and proteins throughout the neuron is essential for the establishment and maintenance of cell morphology and synaptic function. However, the dynamic shape and spatial organization of secretory organelles, and their role in defining neuronal polarity and the composition of synapses, are not well delineated. In particular, the structure and function of the continuous and intricate network of the endoplasmic reticulum (ER) in neurons remain largely unknown. Here we review our current understanding of the ER in dendrites and axons, its contribution to local trafficking of neurotransmitter receptors, and the implications for synaptic plasticity and pathology.
• Proteolytic networks in cancer
  - trends cell biol 21(4):228-237 (2011)
  Proteases are important for multiple processes during malignant progression, including tumor angiogenesis, invasion and metastasis. Recent evidence reveals that tumor-promoting proteases function as part of an extensive multidirectional network of proteolytic interactions, in contrast to the unidirectional caspase cascade. These networks involve different constituents of the tumor microenvironment and key proteases, such as cathepsin B, urokinase-type plasminogen activator and several matrix metalloproteinases, occupy central nodes for amplifying proteolytic signals passing through the network. The proteolytic network interacts with other important signaling pathways in tumor biology, involving chemokines, cytokines, and kinases. Viewing these proteolytic interactions as a system of activating and inhibiting reactions provides insight into tumor biology and reveals relevant pharmaceutical targets. This review examines recent advances in understanding proteases in cance! r and summarizes how the network of activity is co-opted to promote tumor progression.
• Hedgehog morphogen: from secretion to reception
  - trends cell biol 21(4):238-246 (2011)
  A major challenge of developmental biology is to understand how cells coordinate developmental behaviors with their neighbors. To achieve this, cells often employ signaling molecules that emanate from a local source and act at a distance on target cells. The Hedgehog morphogen is an essential signaling molecule required for numerous processes during animal development. Emphasizing the importance of this molecule for both growth control and patterning, Hedgehog signaling activity is often deregulated during cancer formation and progression. The secretion and spread of Hedgehog are not passive processes, but require accessory molecules involved in Hedgehog processing, release, spread and reception. In this review, I focus on the factors that are required to control the spread and activity of Hedgehog, highlighting recent data that have shed light on these processes.
• The mammalian actin-binding protein 1 (mAbp1): a novel molecular player in leukocyte biology
  - trends cell biol 21(4):247-255 (2011)
  The transmittance of force from the actin cytoskeleton via integrins to extracellular ligands is essential for multiple aspects of leukocyte function. In addition, integrins must be efficiently linked to the cytoskeleton in order to resist external forces that act on the cell. Recently, the mammalian actin-binding protein 1 (mAbp1) was identified as a novel adaptor involved in linking adhesion molecules of the β2 integrin family to the actin cytoskeleton, indicating that this protein might have a fundamental impact on leukocyte functions that are associated explicitly with force transmittance; namely, intraluminal adhesion and phagocytosis. Here, we review the current understanding of the molecular and cellular functions of mAbp1 with a focus on its impact in leukocyte biology.

Hot off the presses! Jan 01 trends cell biol

The Jan 01 issue of the trends cell biol is now up on Pubget (About trends cell biol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Contents page + Editorial Board
  - trends cell biol 21(1):i (2011)
  
• Richard Pagano (1944–2010)
  - trends cell biol 21(1):1 (2011)
  
• Dogma bites back – the evidence for branched actin
  - trends cell biol 21(1):2 (2011)
  
• Discussing the morphology of actin filaments in lamellipodia
  - trends cell biol 21(1):2-4 (2011)
  
• Actin networking in lamellipodia and beyond
  - trends cell biol 21(1):4-5 (2011)
  
• The role of chromatin structure in cell migration
  - trends cell biol 21(1):6-11 (2011)
  Chromatin dynamics play a major role in regulating genetic processes. Now, accumulating data suggest that chromatin structure may also affect the mechanical properties of the nucleus and cell migration. Global chromatin organization appears to modulate the shape, the size and the stiffness of the nucleus. Directed-cell migration, which often requires nuclear reshaping to allow passage of cells through narrow openings, is dependent not only on changes in cytoskeletal elements but also on global chromatin condensation. Conceivably, during cell migration a physical link between the chromatin and the cytoskeleton facilitates coordinated structural changes in these two components. Thus, in addition to regulating genetic processes, we suggest that alterations in chromatin structure could facilitate cellular reorganizations necessary for efficient migration.
• Fungal evo–devo: organelles and multicellular complexity
  - trends cell biol 21(1):12-19 (2011)
  Peroxisome-derived Woronin bodies of the Ascomycota phyla, and the endoplasmic reticulum (ER)-derived septal pore cap (SPC) of the Basidiomycota, are both fungal organelles that prevent cytoplasmic bleeding when multicellular hyphal filaments are wounded. Analysis of Woronin body constituent proteins suggests that these organelles evolved in part through gene duplication and co-opting of non-essential genes for new functions, indicating that new organelles can arise through typical evolutionary mechanisms. Interestingly, clades possessing the Woronin body and SPC also produce the largest and most complex multicellular fungal reproductive structures. Certain Woronin body and SPC mutants have defects in growth and development, suggesting functions beyond cellular wound healing. I argue that studying these specialized systems will help to reveal the basis for fungal diversity and provide general principles for co-evolution of organelles and multicellular complexity.
• pH regulation and beyond: unanticipated functions for the voltage-gated proton channel, HVCN1
  - trends cell biol 21(1):20-28 (2011)
  Electrophysiological studies have implicated voltage-gated proton channels in several specific cellular contexts. In neutrophils, they mediate charge compensation that is associated with the oxidative burst of phagocytosis. Molecular characterization of the hydrogen voltage-gated channel 1 (HVCN1) has enabled identification of unanticipated and diverse functions: HVCN1 not only modulates signaling from the B-cell receptor following B-cell activation and histamine release from basophils, but also mediates pH-dependent activation of spermatozoa, as well as acid secretion by tracheal epithelium. The importance of HVCN1 in pH regulation during phagocytosis was established by surprising evidence that indicated its first-responder role. In this review, we discuss recent findings from a functional perspective, and the potential of HVCN1 as a therapeutic target for autoimmune and other diseases.
• The Nebulin family: an actin support group
  - trends cell biol 21(1):29-37 (2011)
  Nebulin, a giant, actin-binding protein, is the largest member of a family of proteins (including N-RAP, nebulette, lasp-1 and lasp-2) that are assembled in a variety of cytoskeletal structures, and expressed in different tissues. For decades, nebulin has been thought to act as a molecular ruler, specifying the precise length of actin filaments in skeletal muscle. However, emerging evidence suggests that nebulin should not be viewed as a ruler but as an actin filament stabilizer required for length maintenance. Nebulin has also been implicated recently in an array of regulatory functions independent of its role in actin filament length regulation. In this review, we discuss the current evolutionary, biochemical, and functional data for the nebulin family of proteins — a family whose members, both large and small, function as cytoskeletal scaffolds and stabilizers.
• Kinetochores' gripping feat: conformational wave or biased diffusion?
  - trends cell biol 21(1):38-46 (2011)
  Climbing up a cliff while the rope unravels underneath your fingers does not sound like a well-planned adventure. Yet chromosomes face a similar challenge during each cell division. Their alignment and accurate segregation depends on staying attached to the assembling and disassembling tips of microtubule fibers. This coupling is mediated by kinetochores, intricate machines that attach chromosomes to an ever-changing microtubule substrate. Two models for kinetochore-microtubule coupling were proposed a quarter century ago: conformational wave and biased diffusion. These models differ in their predictions for how coupling is performed and regulated. The availability of purified kinetochore proteins has enabled biochemical and biophysical analyses of the kinetochore-microtubule interface. Here, we discuss what these studies reveal about the contributions of each model.
• Forcing form and function: biomechanical regulation of tumor evolution
  - trends cell biol 21(1):47-56 (2011)
  Cancer cells exist in a constantly evolving tissue microenvironment of diverse cell types within a proteinaceous extracellular matrix. As tumors evolve, the physical forces within this complex microenvironment change, with pleiotropic effects on both cell- and tissue-level behaviors. Recent work suggests that these biomechanical factors direct tissue development and modulate tissue homeostasis, and, when altered, crucially influence tumor evolution. In this review, we discuss the biomechanical regulation of cell and tissue homeostasis from the molecular, cellular and tissue levels, including how modifications of this physical dialogue could contribute to cancer etiology. Because of the broad impact of biomechanical factors on cell and tissue functions, an understanding of tumor evolution from the biomechanical perspective should improve risk assessment, clinical diagnosis and the efficacy of cancer treatment.
• Common themes in centriole and centrosome movements
  - trends cell biol 21(1):57-66 (2011)
  Centrioles are found in nearly all eukaryotic cells and are required for growth and maintenance of the radial array of microtubules, the mitotic spindle, and cilia and flagella. Different types of microtubule structures are often required at different places in a given cell; centrioles must move around to nucleate these varied structures. Here, we draw together recent data on diverse centriole movements to decipher common themes in how centrioles move. Par proteins establish and maintain the required cellular asymmetry. The actin cytoskeleton facilitates movement of multiple basal bodies. Microtubule forces acting on the cell cortex, and nuclear–cytoskeletal links, are important for positioning individual centrosomes, and during cell division. Knowledge of these common mechanisms can inform the study of centriole movements across biology.

Hot off the presses! Oct 01 Trends Cell Biol

The Oct 01 issue of the Trends Cell Biol is now up on Pubget (About Trends Cell Biol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Editorial Board
  - Trends Cell Biol 21(10):i (2011)
  
• Corrigendum: Long noncoding RNAs and human disease: [Trends in Cell Biology 21 (2011), 354–361]
  - Trends Cell Biol 21(10):561 (2011)
  
• Essence of life: essential genes of minimal genomes
  - Trends Cell Biol 21(10):562-568 (2011)
  Essential genes are absolutely required for cell survival. Determination of the universal minimal set of genes needed to sustain life is, therefore, expected to contribute greatly to our understanding of life at its simplest level, with applications in medicine and synthetic biology. The search for the minimal genome has led to the identification of often variable gene sets. We argue here that, based on the outcome of these analyses, it is becoming increasingly evident that some genes, and the functions encoded by them, are absolutely necessary for the survival of any living entity, whereas others can be omitted. We also examine ways of determining the minimal genome and discuss possible practical applications of a minimal cell.
• Taking a "good" look at free radicals in the aging process
  - Trends Cell Biol 21(10):569-576 (2011)
  The mitochondrial free radical theory of aging (MFRTA) proposes that aging is caused by damage to macromolecules by mitochondrial reactive oxygen species (ROS). This is based on the observed association of the rate of aging and the aged phenotype with the generation of ROS and oxidative damage. However, recent findings, in particular in Caenorhabditis elegans but also in rodents, suggest that ROS generation is not the primary or initial cause of aging. Here, we propose that ROS are tightly associated with aging because they play a role in mediating a stress response to age-dependent damage. This could generate the observed correlation between aging and ROS without implying that ROS damage is the earliest trigger or main cause of aging.
• Axon regeneration mechanisms: insights from C. elegans
  - Trends Cell Biol 21(10):577-584 (2011)
  Understanding the mechanisms of axon regeneration is of great importance to the development of therapeutic treatments for spinal cord injury or stroke. Axon regeneration has long been studied in diverse vertebrate and invertebrate models, but until recently had not been analyzed in the genetically tractable model organism Caenorhabditis elegans. The small size, simple neuroanatomy, and transparency of C. elegans allows single fluorescently labeled axons to be severed in live animals using laser microsurgery. Many neurons in C. elegans are capable of regenerative regrowth, and can in some cases re-establish functional connections. Large-scale genetic screens have begun to elucidate the genetic basis of axon regrowth.
• Central nervous system myelin: structure, synthesis and assembly
  - Trends Cell Biol 21(10):585-593 (2011)
  The wrapping of multiple layers of myelin membrane sheets around an axon is of fundamental importance for the function of the nervous system. In the central nervous system (CNS) oligodendrocytes synthesize tremendous amounts of cellular membrane to form multiple myelin internodes of highly stable membranes with a specific set of tightly packed lipids and proteins. In recent years, mouse mutants have allowed great advances in our understanding of the functional and structural role of many of the major components of myelin. The challenge now is to extend this knowledge to unravel the molecular machinery and mechanisms required to synthesize, assemble and wrap myelin multiple times around an axon at the appropriate developmental time. Such insight will be essential in designing new therapeutic strategies to promote remyelination in demyelinating disorders such as multiple sclerosis.
• Postsynaptic ProSAP/Shank scaffolds in the cross-hair of synaptopathies
  - Trends Cell Biol 21(10):594-603 (2011)
  Intact synaptic homeostasis is a fundamental prerequisite for a healthy brain. Thus, it is not surprising that altered synaptic morphology and function are involved in the molecular pathogenesis of so-called synaptopathies including autism, schizophrenia (SCZ) and Alzheimer's disease (AD). Intriguingly, various recent studies revealed a crucial role of postsynaptic ProSAP/Shank scaffold proteins in all of the aforementioned disorders. Considering these findings, we follow the hypothesis that ProSAP/Shank proteins are key regulators of synaptic development and plasticity with clear-cut isoform-specific roles. We thus propose a model where ProSAP/Shank proteins are in the center of a postsynaptic signaling pathway that is disrupted in several neuropsychiatric disorders.
• Regulation of microtubule dynamics by TOG-domain proteins XMAP215/Dis1 and CLASP
  - Trends Cell Biol 21(10):604-614 (2011)
  The molecular mechanisms by which microtubule-associated proteins (MAPs) regulate the dynamic properties of microtubules (MTs) are still poorly understood. We review recent advances in our understanding of two conserved families of MAPs, the XMAP215/Dis1 and CLASP family of proteins. In vivo and in vitro studies show that XMAP215 proteins act as microtubule polymerases at MT plus ends to accelerate MT assembly, and CLASP proteins promote MT rescue and suppress MT catastrophe events. These are structurally related proteins that use conserved TOG domains to recruit tubulin dimers to MTs. We discuss models for how these proteins might use these individual tubulin dimers to regulate dynamic behavior of MT plus ends.
• Regulating Rap small G-proteins in time and space
  - Trends Cell Biol 21(10):615-623 (2011)
  Signaling by the small G-protein Rap is under tight regulation by its GEFs and GAPs. These are multi-domain proteins that are themselves controlled by distinct upstream pathways, and thus couple different extra- and intracellular cues to Rap. The individual RapGEFs and RapGAPs are, in addition, targeted to specific cellular locations by numerous anchoring mechanisms and, consequently, may control different pools of Rap. Here, we review the various activating signals and targeting mechanisms of these proteins and discuss their contribution to the spatiotemporal regulation and biological functions of the Rap proteins.

Hot off the presses! Oct 01 Trends Cell Biol

The Oct 01 issue of the Trends Cell Biol is now up on Pubget (About Trends Cell Biol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Editorial Board
  - Trends Cell Biol 19(10):i (2009)
  
• The regulation of aging: does autophagy underlie longevity?
  - Trends Cell Biol 19(10):487-494 (2009)
  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 are directly regulated by longevity pathways. These findings support the emerging view that autophagy is a central regulatory mechanism for aging in diverse eukaryotic species.
• Plasmodesmata – bridging the gap between neighboring plant cells
  - Trends Cell Biol 19(10):495-503 (2009)
  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 and function of PD in mediating the trafficking of non-cell-autonomous information macromolecules. Important future challenges are to build a detailed model for the plasmodesmal supramolecular complex and to further elucid! ate the molecular and cellular aspects of this novel plant cell-to-cell communication pathway.
• The Kindlin protein family: new members to the club of focal adhesion proteins
  - Trends Cell Biol 19(10):504-513 (2009)
  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 adhesion proteins, and the crosstalk between cell–cell and cell–matrix adhesions in health and disease.
• Molecular mediators of macrophage fusion
  - Trends Cell Biol 19(10):514-522 (2009)
  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 target areas for future research and medical relevance.
• Chemotaxis: finding the way forward with Dictyostelium
  - Trends Cell Biol 19(10):523-530 (2009)
  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 (PIP3) and other intracellular messengers that connect signalling and migration, and the transition to models of chemotaxis driven by multiple, intertwined signalling pathways. In shallow gradients, pseudopods are generated with random directions, and we discuss how chemotaxis can operate by biasing this process. Overall we describe how Dictyostelium has the potential to unlock ! many fundamental questions in the cell motility field.
• Mitotic phosphatases: from entry guards to exit guides
  - Trends Cell Biol 19(10):531-541 (2009)
  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 and provide novel insights into the dynamic and versatile nature of mitotic phosphoregulation.
• Crosstalk in Met receptor oncogenesis
  - Trends Cell Biol 19(10):542-551 (2009)
  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 resistance.

Hot off the presses! Nov 01 trends cell biol

The Nov 01 issue of the trends cell biol is now up on Pubget (About trends cell biol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Contents page + Editorial Board
  - trends cell biol 20(11):i (2010)
  
• Corrigendum: Acidic calcium stores open for business: expanding the potential for intracellular Ca2+ signaling: [Trends in Cell Biology 20 (2010), 277–286]
  - trends cell biol 20(11):627 (2010)
  
• Dicing with dogma: de-branching the lamellipodium
  - trends cell biol 20(11):628-633 (2010)
  The primary event in the movement of a migrating eukaryotic cell is the extension of cytoplasmic sheets termed lamellipodia composed of networks of actin filaments. Lamellipodia networks are thought to arise through the branching of new filaments from the sides of old filaments, producing a dendritic array. Recent studies by electron tomography have revealed the three dimensional organization of lamellipodia and show, contrary to previous evidence, that actin filaments do not form dendritic arrays in vivo. These findings signal a reconsideration of the structural basis of protrusion and about the roles of the different actin nucleating and elongating complexes involved in the process.
• Timing control in regulatory networks by multisite protein modifications
  - trends cell biol 20(11):634-641 (2010)
  Computational and experimental studies have yielded quantitative insights into the role for multisite phosphorylation, and other protein modifications, in cell function. This work has emphasized the creation of thresholds and switches for cellular decisions. To date, the dynamics of phosphorylation events have been disregarded yet could be equally relevant for cell function. Here, we discuss theoretical predictions about the kinetic functions of multisite phosphorylation in regulatory networks and how these predictions relate to experimental findings. Using DNA replication as an example, we demonstrate that multisite phosphorylations can support coherent origin firing and robustness against rereplication. We suggest that multisite protein modifications provide a molecular mechanism to robustly time cellular events in the cell cycle, the circadian clock and signal transduction.
• Divide and ProsPer: The emerging role of PtdIns3P in cytokinesis
  - trends cell biol 20(11):642-649 (2010)
  Cytokinesis is the final step of cell division whereby the dividing cells separate physically. Failure of this process has been proposed to cause tumourigenesis. Several specific lipids are essential for cytokinesis, and recent evidence has revealed that phosphatidylinositol 3-phosphate (PtdIns3P) — a well-known regulator of endosomal trafficking, receptor signaling, nutrient sensing and autophagy — plays an evolutionarily conserved role during cytokinesis. The emerging picture is that PtdIns3P and its regulators and effectors constitute a novel regulatory mechanism for cytokinesis. Elucidating the role of PtdIns3P in cytokinesis might contribute to insight into mechanisms of tumour development and suppression.
• WASH, WHAMM and JMY: regulation of Arp2/3 complex and beyond
  - trends cell biol 20(11):650-661 (2010)
  Arp2/3 complex mediates the nucleation of actin filaments in multiple subcellular processes, and is activated by nucleation-promoting factors (NPFs) from the Wiskott–Aldrich Syndrome family. In exciting new developments, this family has grown by three members: WASH, WHAMM and JMY, which extend the repertoire of dynamic membrane structures that are remodeled following Arp2/3 activation in vivo. These novel NPFs share an actin- and Arp2/3-interacting WCA module, and combine Arp2/3 activation with additional biochemical functions, including capping protein inhibition, microtubule engagement or Arp2/3-independent actin nucleation, none of which had been previously associated with canonical WCA-harboring proteins. Uncovering the physiological relevance of these unique activities will require concerted efforts from multiple disciplines, and is sure to impact our understanding of how the cytoskeleton controls so many dynamic subcellular events.
• Histone demethylases in development and disease
  - trends cell biol 20(11):662-671 (2010)
  Histone modifications serve as regulatory marks that are instrumental for the control of transcription and chromatin architecture. Strict regulation of gene expression patterns is crucial during development and differentiation, where diverse cell types evolve from common predecessors. Since the first histone lysine demethylase was discovered in 2004, a number of demethylases have been identified and implicated in the control of gene expression programmes and cell fate decisions. Histone demethylases are now emerging as important players in developmental processes and have been linked to human diseases such as neurological disorders and cancer.
• In control at the ER: PTP1B and the down-regulation of RTKs by dephosphorylation and endocytosis
  - trends cell biol 20(11):672-679 (2010)
  Receptor tyrosine kinases (RTKs) control the cellular response to a range of stimuli by binding extracellular factors and transmitting appropriate signals to intracellular sites. Protein tyrosine phosphatase 1B (PTP1B) modulates the activity of several RTKs by directly targeting the phosphorylated tyrosine residues that dictate their signaling output. Interestingly, the phenotypes of PTP1B deficiency in different contexts point to a more complex role in regulating RTK signaling. Exciting recent results indicate that the endocytic down-regulation of RTKs could be directly controlled by PTP1B. Microscopy studies have demonstrated an effect of PTP1B on post-endocytic internalization of RTKs into multivesicular bodies, and specific substrates that could influence their endosomal trafficking have been identified. These findings reveal a novel link between two important mechanisms of RTK signal attenuation and highlight the multifaceted impact of PTP1B on cell signaling.
• Cell cholesterol homeostasis: Mediation by active cholesterol
  - trends cell biol 20(11):680-687 (2010)
  Recent evidence suggests that the major pathways mediating cell cholesterol homeostasis respond to a common signal: active membrane cholesterol. Active cholesterol is the fraction that exceeds the complexing capacity of the polar bilayer lipids. Increments in plasma membrane cholesterol exceeding this threshold have an elevated chemical activity (escape tendency) and redistribute via diverse transport proteins to both circulating plasma lipoproteins and intracellular organelles. Active cholesterol thereby prompts several feedback responses. It is the substrate for its own esterification and for the synthesis of regulatory side-chain oxysterols. It also stimulates manifold pathways that down-regulate the biosynthesis, curtail the ingestion and increase the export of cholesterol. Thus, the abundance of cell cholesterol is tightly coupled to that of its polar lipid partners through active cholesterol.