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  • Prime Editing: A New Way for Genome Editing
    Trends Cell Biol. (IF 16.588) Pub Date : 2020-01-27
    Marek Marzec; Agnieszka Brąszewska-Zalewska; Goetz Hensel

    Precise and efficient use of genome editing tools are hampered by the introduction of DNA double-strand breaks, donor DNA templates, or homology-directed repair. A recent study expands the genome editing toolbox with the introduction of prime editing, which overcomes previous challenges and introduces insertions, deletions, and all putative 12 types of base-to-base conversions in human cells.

  • Subcellular Chemical Imaging: New Avenues in Cell Biology
    Trends Cell Biol. (IF 16.588) Pub Date : 2020-01-24
    Johan Decelle; Giulia Veronesi; Benoit Gallet; Hryhoriy Stryhanyuk; Pietro Benettoni; Matthias Schmidt; Rémi Tucoulou; Melissa Passarelli; Sylvain Bohic; Peta Clode; Niculina Musat

    To better understand the physiology and acclimation capability of the cell, one of the great challenges of the future is to access the interior of a cell and unveil its chemical landscape (composition and distribution of elements and molecules). Chemical imaging has greatly improved in sensitivity and spatial resolution to visualize and quantify nutrients, metabolites, toxic elements, and drugs in single cells at the subcellular level. This review aims to present the current potential of these emerging imaging technologies and to guide biologists towards a strategy for interrogating biological processes at the nanoscale. We also describe various solutions to combine multiple imaging techniques in a correlative way and provide perspectives and future directions for integrative subcellular imaging across different disciplines.

  • Metabolic Regulation of Cell Fate and Function
    Trends Cell Biol. (IF 16.588) Pub Date : 2020-01-23
    Shohini Ghosh-Choudhary; Jie Liu; Toren Finkel

    Increasing evidence implicates metabolic pathways as key regulators of cell fate and function. Although the metabolism of glucose, amino acids, and fatty acids is essential to maintain overall energy homeostasis, the choice of a given metabolic pathway and the levels of particular substrates and intermediates increasingly appear to modulate specific cellular activities. This connection is likely related to the growing appreciation that molecules such as acetyl-CoA act as a shared currency between metabolic flux and chromatin modification. We review recent evidence for a role of metabolism in modulating cellular function in four distinct contexts. These areas include the immune system, the tumor microenvironment, the fibrotic response, and stem cell function. Together, these examples suggest that metabolic pathways do not simply provide the fuel that powers cellular activities but instead help to shape and determine cellular identity.

  • Lipoprotein Lipase Sorting: Sphingomyelin and a Proteoglycan Show the Way
    Trends Cell Biol. (IF 16.588) Pub Date : 2020-01-22
    Vytas A. Bankaitis; Yaxi Wang

    A mechanistic description for how soluble protein cargos are sorted into distinct vesicle classes at the level of the trans-Golgi network (TGN) has remained elusive. In a recent study in Developmental Cell, Sundberg et al. reveal that sphingomyelin and a proteoglycan mediate lipoprotein lipase sorting in the TGN.

  • Viewing Nuclear Architecture through the Eyes of Nocturnal Mammals
    Trends Cell Biol. (IF 16.588) Pub Date : 2020-01-22
    Yana Feodorova; Martin Falk; Leonid A. Mirny; Irina Solovei

    The cell nucleus is a remarkably well-organized organelle with membraneless but distinct compartments of various functions. The largest of them, euchromatin and heterochromatin, are spatially segregated in such a way that the transcriptionally active genome occupies the nuclear interior, whereas silent genomic loci are preferentially associated with the nuclear envelope. This rule is broken by rod photoreceptor cells of nocturnal mammals, in which the two major compartments have inverted positions. The inversion and dense compaction of heterochromatin converts these nuclei into microlenses that focus light and facilitate nocturnal vision. As is often the case in biology, when a mutation helps to understand normal processes and structures, inverted nuclei have served as a tool to unravel general principles of nuclear organization, including mechanisms of heterochromatin tethering to the nuclear envelope, autonomous behavior of small genomic segments, and euchromatin–heterochromatin segregation.

  • Relevance and Regulation of Cell Density
    Trends Cell Biol. (IF 16.588) Pub Date : 2020-01-21
    Gabriel E. Neurohr; Angelika Amon

    Cell density shows very little variation within a given cell type. For example, in humans variability in cell density among cells of a given cell type is 100 times smaller than variation in cell mass. This tight control indicates that maintenance of a cell type-specific cell density is important for cell function. Indeed, pathological conditions such as cellular senescence are accompanied by changes in cell density. Despite the apparent importance of cell-type-specific density, we know little about how cell density affects cell function, how it is controlled, and how it sometimes changes as part of a developmental process or in response to changes in the environment. The recent development of new technologies to accurately measure the cell density of single cells in suspension and in tissues is likely to provide answers to these important questions.

  • Biogenesis and Functions of Circular RNAs Come into Focus
    Trends Cell Biol. (IF 16.588) Pub Date : 2020-01-20
    Mei-Sheng Xiao; Yuxi Ai; Jeremy E. Wilusz

    Many eukaryotic protein-coding genes are able to generate exonic circular RNAs. Most of these covalently linked transcripts are expressed at low levels, but some accumulate to higher levels than their associated linear mRNAs. We highlight several methodologies that have been developed in recent years to identify and characterize these transcripts, and which have revealed an increasingly detailed view of how circular RNAs can be generated and function. It is now clear that modulation of circular RNA levels can result in a variety of molecular and physiological phenotypes, including effects on the nervous system, innate immunity, microRNAs, and many disease-relevant pathways.

  • How the Mitoprotein-Induced Stress Response Safeguards the Cytosol: A Unified View
    Trends Cell Biol. (IF 16.588) Pub Date : 2020-01-18
    Felix Boos; Johnathan Labbadia; Johannes M. Herrmann

    Mitochondrial and cytosolic proteostasis are of central relevance for cellular stress resistance and organismal health. Recently, a number of individual cellular programs were described that counter the fatal consequences of mitochondrial dysfunction. These programs remove arrested import intermediates from mitochondrial protein translocases, stabilize protein homeostasis within mitochondria, and, in particular, increase the levels and activity of chaperones and the proteasome system in the cytosol. Here, we describe the different responses to mitochondrial perturbation and propose to unify the seemingly distinct mitochondrial-cytosolic quality control mechanisms into a single network, the mitoprotein-induced stress response. This holistic view places mitochondrial biogenesis at a central position of the cellular proteostasis network, emphasizing the importance of mitochondrial protein import processes for development, reproduction, and ageing.

  • RIPK1 Kinase-Dependent Death: A Symphony of Phosphorylation Events
    Trends Cell Biol. (IF 16.588) Pub Date : 2020-01-17
    Tom Delanghe; Yves Dondelinger; Mathieu J.M. Bertrand

    The serine/threonine kinase RIPK1 has emerged as a crucial component of the inflammatory response activated downstream of several immune receptors, where it paradoxically functions as a scaffold to protect the cell from death or instead as an active kinase to promote the killing of the cell. While RIPK1 kinase-dependent cell death has revealed its physiological importance in the context of microbial infection, aberrant activation of RIPK1 is also demonstrated to promote cell death-driven inflammatory pathologies, highlighting the importance of fundamentally understanding proper RIPK1 regulation. Recent advances in the field demonstrated the crucial role of phosphorylation in the fine-tuning of RIPK1 activation and, additionally, question the exact mechanism by which RIPK1 enzymatic activity transmits the death signal.

  • When Separation Strengthens Ties
    Trends Cell Biol. (IF 16.588) Pub Date : 2020-01-15
    Helena Canever; François Sipieter; Nicolas Borghi

    Phase separation underlies functional compartmentalization in living systems. Two recent studies (Beutel et al. and Schwayer et al.) show that zonula occludens (ZO) proteins of tight junctions (TJs) condense into compartments within the cytoplasm that display liquid properties. This ability to condense predicts normal TJ assembly and epithelial barrier function which are essential for vertebrate embryogenesis.

  • Protecting the Aging Genome
    Trends Cell Biol. (IF 16.588) Pub Date : 2020-01-06
    Michael A. Petr; Tulika Tulika; Lina M. Carmona-Marin; Morten Scheibye-Knudsen

    Mounting evidence suggests that DNA damage plays a central role in aging. Multiple tiers of defense have evolved to reduce the accumulation of DNA damage, including reducing damaging molecules, repairing DNA damage, and inducing senescence or apoptosis in response to persistent DNA damage. Mutations in or failure of these pathways can lead to accelerated or premature aging and age-related decline in vital organs, supporting the hypothesis that maintaining a pristine genome is paramount for human health. Understanding how we cope with DNA damage could inform on the aging process and further on how deficient DNA maintenance manifests in age-related phenotypes. This knowledge may lead to the development of novel interventions promoting healthspan.

  • Organoid and Assembloid Technologies for Investigating Cellular Crosstalk in Human Brain Development and Disease
    Trends Cell Biol. (IF 16.588) Pub Date : 2019-12-23
    Rebecca M. Marton; Sergiu P. Pașca

    The biology of the human brain, and in particular the dynamic interactions between the numerous cell types and regions of the central nervous system, has been difficult to study due to limited access to functional brain tissue. Technologies to derive brain organoids and assembloids from human pluripotent stem cells are increasingly utilized to model, in progressively complex preparations, the crosstalk between cell types in development and disease. Here, we review the use of these human cellular models to study cell–cell interactions among progenitors, neurons, astrocytes, oligodendrocytes, cancer cells, and non-central nervous system cell types, as well as efforts to study connectivity between brain regions following controlled assembly of organoids. Ultimately, the promise of these patient-derived preparations is to uncover previously inaccessible features of brain function that emerge from complex cell–cell interactions and to improve our mechanistic understanding of neuropsychiatric disorders.

  • Epigenetic Regulation of Mesenchymal Stem Cell Homeostasis
    Trends Cell Biol. (IF 16.588) Pub Date : 2019-12-20
    Bing-Dong Sui; Chen-Xi Zheng; Meng Li; Yan Jin; Cheng-Hu Hu

    Mesenchymal stem cells (MSCs) have putative roles in maintaining adult tissue health, and the functional decline of MSCs has emerged as a crucial pathophysiological driver of various diseases. Epigenetic regulation is essential for establishing and preserving MSC homeostasis in vivo. Furthermore, growing evidence suggests that epigenetic dysregulation contributes to age- and disease-associated MSC alterations. Epigenetic marks in MSCs can be amplified through self-renewal divisions and transmitted to differentiated progeny, further perpetuating their role in tissue maintenance and pathogenesis. We review the epigenetic regulation of MSC homeostasis, emphasizing its contributions to organismal health and disease. Understanding these epigenetic mechanisms could hold promise as targets for MSC-mediated regenerative therapies.

  • Mobility and Repair of Damaged DNA: Random or Directed?
    Trends Cell Biol. (IF 16.588) Pub Date : 2019-12-10
    Roxanne Oshidari, Karim Mekhail, Andrew Seeber

    The increased mobility of damaged DNA within the nucleus can promote genome stability and cell survival. New cell biology approaches have indicated that damaged DNA mobility exhibits random and directed movements during DNA repair. Here, we review recent studies that collectively reveal that cooperation between different molecular mechanisms, which underlie increases in the random and directional motion of damaged DNA, can promote genome repair. We also review the latest approaches that can be used to distinguish between random and directed motions of damaged DNA or other biological molecules. Detailed understanding of the mechanisms behind the increased motion of damaged DNA within the nucleus will reveal more of the secrets of genome organization and stability while potentially pointing to novel research and therapeutic tools.

  • Squeezing in a Meal: Myosin Functions in Phagocytosis
    Trends Cell Biol. (IF 16.588) Pub Date : 2019-12-10
    Sarah R. Barger, Nils C. Gauthier, Mira Krendel

    Phagocytosis is a receptor-mediated, actin-dependent process of internalization of large extracellular particles, such as pathogens or apoptotic cells. Engulfment of phagocytic targets requires the activity of myosins, actin-dependent molecular motors, which perform a variety of functions at distinct steps during phagocytosis. By applying force to actin filaments, the plasma membrane, and intracellular proteins and organelles, myosins can generate contractility, directly regulate actin assembly to ensure proper phagocytic internalization, and translocate phagosomes or other cargo to appropriate cellular locations. Recent studies using engineered microenvironments and phagocytic targets have demonstrated how altering the actomyosin cytoskeleton affects phagocytic behavior. Here, we discuss how studies using genetic and biochemical manipulation of myosins, force measurement techniques, and live-cell imaging have advanced our understanding of how specific myosins function at individual steps of phagocytosis.

  • Coupling DNA Damage and Repair: an Essential Safeguard during Programmed DNA Double-Strand Breaks?
    Trends Cell Biol. (IF 16.588) Pub Date : 2019-12-06
    Mireille Bétermier, Valérie Borde, Jean-Pierre de Villartay

    DNA double-strand breaks (DSBs) are the most toxic DNA lesions given their oncogenic potential. Nevertheless, programmed DSBs (prDSBs) contribute to several biological processes. Formation of prDSBs is the ‘price to pay’ to achieve these essential biological functions. Generated by domesticated PiggyBac transposases, prDSBs have been integrated in the life cycle of ciliates. Created by Spo11 during meiotic recombination, they constitute a driving force of evolution and ensure balanced chromosome content for successful reproduction. Produced by the RAG1/2 recombinase, they are required for the development of the adaptive immune system in many species. The coevolution of processes that couple introduction of prDSBs to their accurate repair may constitute an effective safeguard against genomic instability.

  • Splicing Busts a Move: Isoform Switching Regulates Migration
    Trends Cell Biol. (IF 16.588) Pub Date : 2019-12-03
    Mithun Mitra, Ha Neul Lee, Hilary A. Coller

    Cell migration is essential for normal development, neural patterning, pathogen eradication, and cancer metastasis. Pre-mRNA processing events such as alternative splicing and alternative polyadenylation result in greater transcript and protein diversity as well as function and activity. A critical role for alternative pre-mRNA processing in cell migration has emerged in axon outgrowth during neuronal development, immune cell migration, and cancer metastasis. These findings suggest that migratory signals result in expression changes of post-translational modifications of splicing or polyadenylation factors, leading to splicing events that generate promigratory isoforms. We summarize this recent progress and suggest emerging technologies that may facilitate a deeper understanding of the role of alternative splicing and polyadenylation in cell migration.

  • The Hippo Pathway, YAP/TAZ, and the Plasma Membrane
    Trends Cell Biol. (IF 16.588) Pub Date : 2019-12-02
    Valentina Rausch, Carsten G. Hansen

    The plasma membrane allows the cell to sense and adapt to changes in the extracellular environment by relaying external inputs via intracellular signaling networks. One central cellular signaling pathway is the Hippo pathway, which regulates homeostasis and plays chief roles in carcinogenesis and regenerative processes. Recent studies have found that mechanical stimuli and diffusible chemical components can regulate the Hippo pathway primarily through receptors embedded in the plasma membrane. Morphologically defined structures within the plasma membrane, such as cellular junctions, focal adhesions, primary cilia, caveolae, clathrin-coated pits, and plaques play additional key roles. Here, we discuss recent evidence highlighting the importance of these specialized plasma membrane domains in cellular feedback via the Hippo pathway.

  • Nicotinamide Nucleotide Transhydrogenase as a Sensor of Mitochondrial Biology
    Trends Cell Biol. (IF 16.588) Pub Date : 2019-11-18
    Salvatore Nesci, Fabiana Trombetti, Alessandra Pagliarani

    The enzyme nicotinamide nucleotide transhydrogenase (NNT) transfers hydride from NADH to NADP+ coupled to H+ translocation across the inner mitochondrial membrane. In a recent study, Kampjut and Sazanov reveal that the bifunctional NNT mechanism rules the NAD(P)+/NAD(P)H interconversion ratio, which in turn regulates antioxidant defense and sirtuin actions.

  • Mechanisms for Active Regulation of Biomolecular Condensates
    Trends Cell Biol. (IF 16.588) Pub Date : 2019-11-18
    Johannes Söding, David Zwicker, Salma Sohrabi-Jahromi, Marc Boehning, Jan Kirschbaum

    Liquid–liquid phase separation is a key organizational principle in eukaryotic cells, on par with intracellular membranes. It allows cells to concentrate specific proteins into condensates, increasing reaction rates and achieving switch-like regulation. We propose two active mechanisms that can explain how cells regulate condensate formation and size. In both, the cell regulates the activity of an enzyme, often a kinase, that adds post-translational modifications to condensate proteins. In enrichment inhibition, the enzyme enriches in the condensate and weakens interactions, as seen in stress granules (SGs), Cajal bodies, and P granules. In localization-induction, condensates form around immobilized enzymes that strengthen interactions, as observed in DNA repair, transmembrane signaling, and microtubule assembly. These models can guide studies into the many emerging roles of biomolecular condensates.

  • Controlling Immunity and Inflammation through Integrin-Dependent Regulation of TGF-β
    Trends Cell Biol. (IF 16.588) Pub Date : 2019-11-16
    Martijn Nolte, Coert Margadant

    Integrins promote cell adhesion and migration, but also control local activation of latent transforming growth factor (TGF)-β contained in extracellular matrix or cell-surface reservoirs. Integrin-dependent activation of TGF-β has emerged as a crucial mechanism whereby tissue-borne cells instruct circulating and resident immune cells. Moreover, this regulation has wide pathophysiological implications in wound healing, tissue fibrosis, antibody production, pathogen clearance, inflammation, autoimmunity, cancer, and possibly metabolic disorders including diabetes. Here we review the spatiotemporal control of TGF-β activation by integrins, and its effects on immune cell signaling and function. We discuss the underlying molecular and cell-biological mechanisms, the implications for human health and disease, and possibilities for future therapeutic exploitation.

  • Wnt Signaling in 3D: Recent Advances in the Applications of Intestinal Organoids
    Trends Cell Biol. (IF 16.588) Pub Date : 2019-11-09
    Alessandra Merenda, Nicola Fenderico, Madelon M. Maurice

    Intestinal organoids grown from adult stem cells have emerged as prototype 3D organotypic models for studying tissue renewal and homeostasis. Owing to their strict dependence on Wnt signaling, intestinal organoids offer an unprecedented opportunity to examine Wnt pathway regulation in normal physiology and cancer. We review how alterations in growth factor dependency and organoid morphology can be exploited to identify Wnt signaling mechanisms, characterize mutated pathway components, and predict responses of patient-derived tumors to targeted therapy. We discuss current deficits in the understanding of genotype–phenotype relationships that are to be considered when interpreting mutation-induced changes in organoid morphology.

  • Reconstructing the Vascular Developmental Milieu In Vitro
    Trends Cell Biol. (IF 16.588) Pub Date : 2019-11-09
    Michael R. Blatchley, Sharon Gerecht

    Understanding human development has fascinated scientists for centuries. With advancements in stem cell technologies, this understanding has expanded beyond fascination to application towards informing the design of therapeutics in regenerative medicine. A focus on establishing a better grasp of the physicochemical cues governing differentiation and tissue assembly has continually enhanced engineered systems to an unprecedented level of biomimicry and, in doing so, has allowed the design of novel therapeutics. The vasculature has a critical role during early stages of development and regeneration events, and is responsive to a range of dynamic environmental cues. In this review, we present biomaterials systems capable of spatially and temporally controlling environmental signals that guide vascular fate and assembly, thereby further informing our understanding of differentiation schema.

  • The UFMylation System in Proteostasis and Beyond
    Trends Cell Biol. (IF 16.588) Pub Date : 2019-11-06
    Yannis Gerakis, Michaela Quintero, Honglin Li, Claudio Hetz

    Post-translational modifications are at the apex of cellular communication and eventually regulate every aspect of life. The identification of new post-translational modifiers is opening alternative avenues in understanding fundamental cell biology processes and may ultimately provide novel therapeutic opportunities. The ubiquitin-fold modifier 1 (UFM1) is a post-translational modifier discovered a decade ago but its biological significance has remained mostly unknown. The field has recently witnessed an explosion of research uncovering the implications of the pathway to cellular homeostasis in living organisms. We overview recent advances in the function and regulation of the UFM1 pathway, and its implications for cell physiology and disease.

  • Laminins in Cellular Differentiation
    Trends Cell Biol. (IF 16.588) Pub Date : 2019-11-05
    Lynn Yap, Hwee Goon Tay, Mien T.X. Nguyen, Monica S. Tjin, Karl Tryggvason

    Basement membrane laminins (LNs) have been shown to modulate cellular phenotypes and differentiation both in vitro and during organogenesis in vivo. At least 16 laminin isoforms are present in mammals, and most are available as recombinant proteins. Ubiquitous LN511 and LN521 promote the clonal derivation and expansion of pluripotent embryonic stem cells (ESCs), and, together with other highly cell type-specific laminins, they can support the differentiation of stem cells into, for example, cardiac muscle fibers, retinal pigmented epithelial (RPE) cells and photoreceptors, dopamine (DA) neurons, and skin keratinocytes. The laminin-supported differentiation methods are highly reproducible and can be made chemically defined and fully xeno-free – a prerequisite for preparing therapeutic stem cell-derived cells. In this review we describe recent work on the use of laminin-based cell culture matrices in stem cell differentiation.

  • COP1 - from plant photomorphogenesis to mammalian tumorigenesis.
    Trends Cell Biol. (IF 16.588) Pub Date : 2005-10-04
    Chunling Yi,Xing Wang Deng

    The COP1 (constitutive photomorphogenic 1) protein, comprising RING finger, coiled-coil and WD40 domains, is conserved in both higher plants and vertebrates. In plants, COP1 acts as an E3 ubiquitin ligase to repress light signaling by targeting photoreceptors and downstream transcription factors for ubiquitylation and degradation. The activity of COP1 in plant cells correlates with its cytoplasmic and nuclear partitioning according to dark or light conditions. In addition, various signaling molecules have been shown to directly interact with COP1 and modulate its activity. Recently, scientists have begun to probe the function and regulation of COP1 in mammalian systems. Initial studies have pointed at possible roles for mammalian COP1 in tumorigenesis and the stress response through regulating the activities of p53 and c-Jun.

  • Regulation of actin cytoskeleton dynamics by Arf-family GTPases.
    Trends Cell Biol. (IF 16.588) Pub Date : 2008-03-11
    Kenneth R Myers,James E Casanova

    Small GTPases of the Arf family are best known for their role in vesicular transport, wherein they nucleate the assembly of coat proteins at sites of carrier vesicle formation. However, accumulating evidence indicates that the Arfs are also important regulators of actin cytoskeleton dynamics and are involved in a variety of actin-based processes, including cell adhesion, migration and neurite outgrowth. The mechanisms of this regulation are remarkably diverse, ranging from the integration of vesicular transport with cytoskeleton assembly to the direct regulation of Rho-family GTPase function. Here, we review recent progress in our understanding of how Arfs and their interacting proteins function to integrate membrane and cytoskeletal dynamics.

  • The spindle checkpoint: tension versus attachment.
    Trends Cell Biol. (IF 16.588) Pub Date : 2005-08-09
    Benjamin A Pinsky,Sue Biggins

    The spindle checkpoint ensures the fidelity of chromosome segregation by preventing cell-cycle progression until all the chromosomes make proper bipolar attachments to the mitotic spindle and come under tension. Despite significant advances in our understanding of spindle checkpoint function, the primary signal that activates the spindle checkpoint remains unclear. Whereas some experiments indicate that the checkpoint recognizes the lack of microtubule attachment to the kinetochore, others indicate that the checkpoint senses the absence of tension generated on the kinetochore by microtubules. The interdependence between tension and microtubule attachment make it difficult to determine whether these signals are separable. In this article (which is part of the Chromosome Segregation and Aneuploidy series), we consider recent evidence that supports and opposes the hypothesis that defects in tension act as the primary checkpoint signal.

  • A Tribute to Chris Marshall.
    Trends Cell Biol. (IF 16.588) Pub Date : 2016-02-02
    Sally J Leevers

  • Connecting to the proteasome
    Trends Cell Biol. (IF 16.588) Pub Date : 2000-12-21

  • Hints for a cure in a muscular dystrophy variant
    Trends Cell Biol. (IF 16.588) Pub Date : 2000-12-21

  • 更新日期:2019-11-01
  • A KID's game of tug o' war
    Trends Cell Biol. (IF 16.588) Pub Date : 2000-12-21

  • Where do golgi residents reside?
    Trends Cell Biol. (IF 16.588) Pub Date : 2000-12-21
    de Boer J

  • Membrane fusion in a nutshell
    Trends Cell Biol. (IF 16.588) Pub Date : 2000-12-21

  • The unpredictability of PI 3-kinase
    Trends Cell Biol. (IF 16.588) Pub Date : 2000-10-26

  • Liberating sleeping beauties by cutting the hook
    Trends Cell Biol. (IF 16.588) Pub Date : 2000-10-26

  • Visions of IFT
    Trends Cell Biol. (IF 16.588) Pub Date : 2000-10-26

  • 更新日期:2019-11-01
  • It takes (more than) two to tango
    Trends Cell Biol. (IF 16.588) Pub Date : 2000-10-26

  • Gone with the wnts
    Trends Cell Biol. (IF 16.588) Pub Date : 2000-10-26

  • Author correction
    Trends Cell Biol. (IF 16.588) Pub Date : 2000-09-22

  • Developments at trends in cell biology
    Trends Cell Biol. (IF 16.588) Pub Date : 2000-09-22

  • Author correction
    Trends Cell Biol. (IF 16.588) Pub Date : 2001-02-07

  • An interview with Randy Schekman and Thomas Südhof.
    Trends Cell Biol. (IF 16.588) Pub Date : 2014-02-12
    Randy Schekman,Thomas Südhof

  • Microscopy and the world wide web.
    Trends Cell Biol. (IF 16.588) Pub Date : 1996-01-01
    C J Jefferies

  • 更新日期:2019-11-01
  • Mitosis in motion.
    Trends Cell Biol. (IF 16.588) Pub Date : 1996-01-01
    J Raff,V Allan

  • Telomere functions: lessons from yeast.
    Trends Cell Biol. (IF 16.588) Pub Date : 1996-01-01
    V A Zakian

    Telomeres are specialized DNA protein structures that form the ends of eukaryotic chromosomes. In yeast, loss of even a single telomere causes a prolonged, but transitory, cell-cycle arrest. During this arrest, many broken chromosomes acquire a new telomere by one of three pathways, although at the cost of a partial loss of heterozygosity. In addition, a substantial fraction of the chromosomes lacking a telomere is lost, which generates an aneuploid cell. In these cases, the broken chromosome is usually replicated and segregated for ten or more cell divisions in unstable form. Extrapolation from yeast suggests that the gradual loss of telomeric DNA that accompanies ageing in humans may initiate the kinds of chromosomal rearrangements and genetic changes that are associated with tumorigenesis.

  • Meiotic metaphase arrest in animal oocytes: its mechanisms and biological significance.
    Trends Cell Biol. (IF 16.588) Pub Date : 1996-01-01
    N Sagata

    Metaphase arrest in meiosis I or II before fertilization is a common and unique feature of oogenesis in many animal species. How and why oocytes from many species are arrested at metaphase, rather than after the completion of meiosis, has long remained a mystery. This article reviews recent advances in our understanding of the mechanisms and biological significance of meiotic metaphase arrest in animal oocytes.

  • Semaphorins: mediators of repulsive growth cone guidance.
    Trends Cell Biol. (IF 16.588) Pub Date : 1996-01-01
    A L Kolodkin

    During development, neuronal growth cones encounter a variety of guidance cues while mediating axon path finding, target recognition and synapse formation. It is clear that repulsive guidance mechanisms play an essential role in these processes. The semaphorin gene family, which is conserved from invertebrates to mammals, includes members that mediate repulsive guidance. Molecular and cellular analysis of this gene family is providing insight into how inhibitory cues function during neurodevelopment.

  • Portals of entry: uncovering HIV nuclear transport pathways.
    Trends Cell Biol. (IF 16.588) Pub Date : 1996-01-01
    M Stevenson

    The ability to infect non-dividing cells sets aside lentiviruses such as HIM from the animal onco-retroviruses which are only able to infect actively dividing cells. This difference in lentivirus and oncovirus biology can be attributed to the relative ability of the reverse transcription complex (preintegration complex) of the virus to enter the nucleus. For lentiviruses such as HIV, active transport processes facilitate this translocation. By contrast, nuclear membrane breakdown at mitosis is required before the reverse transcription complex o f onco-retroviruses can enter the nucleus. Several components o f the HIV reverse transcription complex that facilitate its nuclear transport have now been identified and an analysis o f these import factors is yielding insight into how opposing targeting functions o f viral proteins are regulated.

  • Insulin receptor substrate 1 and 2 (IRS1 and IRS2): what a tangled web we weave.
    Trends Cell Biol. (IF 16.588) Pub Date : 1996-01-01
    S B Waters,J E Pessin

    The insulin receptor is a transmembrane tyrosine kinase that is essential for mediating multiple intracellular signalling cascades that lead ultimately to the biological actions of insulin Tyrosine phosphorylation o f the cytosolic proteins insulin receptor substrate 1 and 2 (IRS1 and IRS2) produces protein 'scaffolding' for the assembly of effector proteins containing Src homology 2 (SH2) domains, thereby generating multisubunit signalling complexes. Although IRS1 was originally isolated as a specific insulin receptor substrate, both IRS1 and IRS2 appear to play a broader role, functioning also as proximal substrates in growth hormone and cytokine receptor signalling. Current data establish IRS1 and IRS2 as critical effectors integrating various cell-type-specific signals into distinct, but overlapping, biological responses.

  • Viruses: the Trojan horses of the cell.
    Trends Cell Biol. (IF 16.588) Pub Date : 1996-01-01
    D Goldfarb

  • Sphingolipid synthesis and membrane formation by Plasmodium.
    Trends Cell Biol. (IF 16.588) Pub Date : 1996-10-01
    K Haldar

    Plasmodium falciparum is a protozoan parasite that causes the most virulent o f human malarias. The asexual blood-stage organism invades and multiplies in a vacuole in the mature erythrocyte. During intravacuolar growth, it induces the formation of a novel network o f tubovesicular membranes, the TVM, that is not present in uninfected red blood cells. Recent data suggest that sphingomyelin biosynthesis by the parasite is an essential requirement for the assembly o f the TVM. Furthermore, sphingolipid synthesis as well as the formation and function o f the TVM may provide new targets for chemotherapy against malaria parasites.

  • Chemical inhibitors of cyclin-dependent kinases.
    Trends Cell Biol. (IF 16.588) Pub Date : 1996-10-01
    L Meijer

    Transient activation o f cyclin-dependent kinases (CDKs) is responsible for transition through the successive phases of the cell-division cycle. Major changes in the expression and regulation of CDKs have been described in human tumours. Enzymatic screening is starting to uncover chemical inhibitors o f CDKs that arrest the cell cycle at various steps. This review summarizes our knowledge of the first generation inhibitors, their molecular mechanisms of action and their effects on the cell cycle and apoptosis, and discusses their potential as synchronizing agents, as ligands for affinity chromatography and as therapeutic agents.

  • A question of balance: the role of cyclin-kinase inhibitors in development and tumorigenesis.
    Trends Cell Biol. (IF 16.588) Pub Date : 1996-10-01
    S J Elledge,J Winston,J W Harper

    Cyclin-kinase inhibitors (CKIs) are versatile negative regulators of cell proliferation that function in developmental decisions, checkpoint control and tumour suppression. Phenotypic examination of mice lacking individual CKIs has begun to reveal the specialized roles that each of these proteins play in vivo. This review focuses on what has been learned about the role of CKIs in development and cancer through the generation of knockout animals. The authors discuss whether differences in knockout phenotypes between CKIs reflect differential use of these inhibitors by the organism or a fundamental difference between the inhibitors, and suggest a balance hypothesis to explain the different effects observed.

  • Cortical domains and the mechanisms of asymmetric cell division.
    Trends Cell Biol. (IF 16.588) Pub Date : 1996-10-01
    P Gönczy,A A Hyman

    Asymmetric cell divisions are central to the generation of cell-fate diversity because factors that are present in a mother cell and distributed unequally at cell division can generate distinct daughters. The process o f asymmetric cell division can be described as consisting of three steps: setting up an asymmetric cue in the mother cell, localizing factors with respect to this cue, and positioning the plane o f cell division so that localized factors are partitioned asymmetrically between daughters. This review describes how specialized cortical domains play a key role in each of these steps and discusses our current understanding of the molecular nature o f cortical domains and the mechanisms by which they may orchestrate asymmetric cell divisions.

  • 更新日期:2019-11-01
  • The subunit-exchange model of histone acetylation.
    Trends Cell Biol. (IF 16.588) Pub Date : 1996-10-01
    S Y Roth,C D Allis

    Increased histone acetylation has long been linked to gene activation, but little is known about how acetylation levels are regulated, largely because the histone acetyltransferase activities (HATs) responsible for this modification have been cloned only recently. Comparison of the biochemical nature of the Tetrahymena HAT A complex with the genetic and biochemical properties of the Saccharomyces Gcn5p-Ado complex leads us to propose that histone acetylase assemblies may be modular in nature and that this modularity may be an intimate part of the association of these enzymes with chromatin. The 'subunit-exchange' model provides a mechanism for the regulation and targeting of both histone acetylases and deacetylases and has implications for the control of cell growth, proliferation and tumorigenesis.

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