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  • Sex and Gender Differences in the Outcomes of Vaccination over the Life Course
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Katie L. Flanagan, Ashley L. Fink, Magdalena Plebanski, Sabra L. Klein

    Both sex (i.e., biological differences) and gender (i.e., social or cultural influences) impact vaccine acceptance, responses, and outcomes. Clinical data illustrate that among children, young adults, and aged individuals, males and females differ in vaccine-induced immune responses, adverse events, and protection. Although males are more likely to receive vaccines, following vaccination, females typically develop higher antibody responses and report more adverse effects of vaccination than do males. Human, nonhuman animal, and in vitro studies reveal numerous immunological, genetic, hormonal, and environmental factors that differ between males and females and contribute to sex- and gender-specific vaccine responses and outcomes. Herein, we address the impact of sex and gender variables that should be considered in preclinical and clinical studies of vaccines.

    更新日期:2017-10-24
  • The FLC Locus: A Platform for Discoveries in Epigenetics and Adaptation
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Charles Whittaker, Caroline Dean

    Our understanding of the detailed molecular mechanisms underpinning adaptation is still poor. One example for which mechanistic understanding of regulation has converged with studies of life history variation is Arabidopsis thaliana FLOWERING LOCUS C (FLC). FLC determines the need for plants to overwinter and their ability to respond to prolonged cold in a process termed vernalization. This review highlights how molecular analysis of vernalization pathways has revealed important insight into antisense-mediated chromatin silencing mechanisms that regulate FLC. In turn, such insight has enabled molecular dissection of the diversity in vernalization across natural populations of A. thaliana. Changes in both cotranscriptional regulation and epigenetic silencing of FLC are caused by noncoding polymorphisms at FLC. The FLC locus is therefore providing important concepts for how noncoding transcription and chromatin regulation influence gene expression and how these mechanisms can vary to underpin adaptation in natural populations.

    更新日期:2017-10-24
  • How Single-Cell Genomics Is Changing Evolutionary and Developmental Biology
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    John C. Marioni, Detlev Arendt

    The recent flood of single-cell data not only boosts our knowledge of cells and cell types, but also provides new insight into development and evolution from a cellular perspective. For example, assaying the genomes of multiple cells during development reveals developmental lineage trees—the kinship lineage—whereas cellular transcriptomes inform us about the regulatory state of cells and their gradual restriction in potency—the Waddington lineage. Beyond that, the comparison of single-cell data across species allows evolutionary changes to be tracked at all stages of development from the zygote, via different kinds of stem cells, to the differentiating cells. We discuss recent insights into the evolution of stem cells and initial attempts to reconstruct the evolutionary cell type tree of the mammalian forebrain, for example, by the comparative analysis of neuron types in the mesencephalic floor. These studies illustrate the immense potential of single-cell genomics to open up a new era in developmental and evolutionary research.

    更新日期:2017-10-24
  • Unconventional or Preset αβ T Cells: Evolutionarily Conserved Tissue-Resident T Cells Recognizing Nonpeptidic Ligands
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Francois Legoux, Marion Salou, Olivier Lantz

    A majority of T cells bearing the αβ T cell receptor (TCR) are specific for peptides bound to polymorphic classical major histocompatibility complex (MHC) molecules. Smaller subsets of T cells are reactive toward various nonpeptidic ligands associated with nonpolymorphic MHC class-Ib (MHC-Ib) molecules. These cells have been termed unconventional for decades, even though only the composite antigen is different from the one seen by classical T cells. Herein, we discuss the identity of these particular T cells in light of the coevolution of their TCR and MHC-Ib restricting elements. We examine their original thymic development: selection on hematopoietic cells leading to the acquisition of an original differentiation program. Most of these cells acquire memory cell features during thymic maturation and exhibit unique patterns of migration into peripheral nonlymphoid tissues to become tissue resident. Thus, these cells are termed preset T cells, as they also display a variety of effector functions. They may act as microbial or danger sentinels, fight microbes, or regulate tissue homeostasis.

    更新日期:2017-10-24
  • Lipid Droplet Biogenesis
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Tobias C. Walther, Jeeyun Chung, Robert V. Farese Jr.

    Lipid droplets (LDs) are ubiquitous organelles that store neutral lipids for energy or membrane synthesis and act as hubs for metabolic processes. Cells generate LDs de novo, converting cells to emulsions with LDs constituting the dispersed oil phase in the aqueous cytoplasm. Here we review our current view of LD biogenesis. We present a model of LD formation from the ER in distinct steps and highlight the biology of proteins that govern this biophysical process. Areas of incomplete knowledge are identified, as are connections with physiology and diseases linked to alterations in LD biology.

    更新日期:2017-10-24
  • Proteostatic Tactics in the Strategy of Sterol Regulation
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Margaret A. Wangeline, Nidhi Vashistha, Randolph Y. Hampton

    In eukaryotes, the synthesis and uptake of sterols undergo stringent multivalent regulation. Both individual enzymes and transcriptional networks are controlled to meet changing needs of the many sterol pathway products. Regulation is tailored by evolution to match regulatory constraints, which can be very different in distinct species. Nevertheless, a broadly conserved feature of many aspects of sterol regulation is employment of proteostasis mechanisms to bring about control of individual proteins. Proteostasis is the set of processes that maintain homeostasis of a dynamic proteome. Proteostasis includes protein quality control pathways for the detection, and then the correction or destruction, of the many misfolded proteins that arise as an unavoidable feature of protein-based life. Protein quality control displays not only the remarkable breadth needed to manage the wide variety of client molecules, but also extreme specificity toward the misfolded variants of a given protein. These features are amenable to evolutionary usurpation as a means to regulate proteins, and this approach has been used in sterol regulation. We describe both well-trod and less familiar versions of the interface between proteostasis and sterol regulation and suggest some underlying ideas with broad biological and clinical applicability.

    更新日期:2017-10-24
  • Coping with Protein Quality Control Failure
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Esther Pilla, Kim Schneider, Anne Bertolotti

    Cells and organisms have evolved numerous mechanisms to cope with and to adapt to unexpected challenges and harsh conditions. Proteins are essential to perform the vast majority of cellular and organismal functions. To maintain a healthy proteome, cells rely on a network of factors and pathways collectively known as protein quality control (PQC) systems, which not only ensure that newly synthesized proteins reach a functional conformation but also are essential for surveillance, prevention, and rescue of protein defects. The main players of PQC systems are chaperones and protein degradation systems: the ubiquitin-proteasome system and autophagy. Here we provide an integrated overview of the diverse PQC systems in eukaryotic cells in health and diseases, with an emphasis on the key regulatory aspects and their cross talks. We also highlight how PQC regulation may be exploited for potential therapeutic benefit.

    更新日期:2017-10-24
  • Mechanisms of Tail-Anchored Membrane Protein Targeting and Insertion
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Un Seng Chio, Hyunju Cho, Shu-ou Shan

    Proper localization of membrane proteins is essential for the function of biological membranes and for the establishment of organelle identity within a cell. Molecular machineries that mediate membrane protein biogenesis need to not only achieve a high degree of efficiency and accuracy, but also prevent off-pathway aggregation events that can be detrimental to cells. The posttranslational targeting of tail-anchored proteins (TAs) provides tractable model systems to probe these fundamental issues. Recent advances in understanding TA-targeting pathways reveal sophisticated molecular machineries that drive and regulate these processes. These findings also suggest how an interconnected network of targeting factors, cochaperones, and quality control machineries together ensures robust membrane protein biogenesis.

    更新日期:2017-10-24
  • In Search of Lost Small Peptides
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Serge Plaza, Gerben Menschaert, François Payre

    A large body of evidence indicates that genome annotation pipelines have biased our view of coding sequences because they generally undersample small proteins and peptides. The recent development of genome-wide translation profiling reveals the prevalence of small/short open reading frames (smORFs or sORFs), which are scattered over all classes of transcripts, including both mRNAs and presumptive long noncoding RNAs. Proteomic approaches further confirm an unexpected variety of smORF-encoded peptides (SEPs), representing an overlooked reservoir of bioactive molecules. Indeed, functional studies in a broad range of species from yeast to humans demonstrate that SEPs can harbor key activities for the control of development, differentiation, and physiology. Here we summarize recent advances in the discovery and functional characterization of smORF/SEPs and discuss why these small players can no longer be ignored with regard to genome function.

    更新日期:2017-10-24
  • Structural and Mechanistic Insights into Protein Translocation
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Tom A. Rapoport, Long Li, Eunyong Park

    Many proteins are translocated across the endoplasmic reticulum (ER) membrane in eukaryotes or the plasma membrane in prokaryotes. These proteins use hydrophobic signal sequences or transmembrane (TM) segments to trigger their translocation through the protein-conducting Sec61/SecY channel. Substrates are first directed to the channel by cytosolic targeting factors, which use hydrophobic pockets to bind diverse signal and TM sequences. Subsequently, these hydrophobic sequences insert into the channel, docking into a groove on the outside of the lateral gate of the channel, where they also interact with lipids. Structural data and biochemical experiments have elucidated how channel partners, the ribosome in cotranslational translocation, and the eukaryotic ER chaperone BiP or the prokaryotic cytosolic SecA ATPase in posttranslational translocation move polypeptides unidirectionally across the membrane. Structures of auxiliary components of the bacterial translocon, YidC and SecD/F, provide additional insight. Taken together, these recent advances result in mechanistic models of protein translocation.

    更新日期:2017-10-24
  • Ribosomal Stalling During Translation: Providing Substrates for Ribosome-Associated Protein Quality Control
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Claudio A.P. Joazeiro

    Cells of all organisms survey problems during translation elongation, which may happen as a consequence of mRNA aberrations, inefficient decoding, or other sources. In eukaryotes, ribosome-associated quality control (RQC) senses elongation-stalled ribosomes and promotes dissociation of ribosomal subunits. This so-called ribosomal rescue releases the mRNA for degradation and allows 40S subunits to be recycled for new rounds of translation. However, the nascent polypeptide chains remain linked to tRNA and associated with the rescued 60S subunits. As a final critical step in this pathway, the Ltn1/Listerin E3 ligase subunit of the RQC complex (RQCc) ubiquitylates the nascent chain, which promotes clearance of the 60S subunit while simultaneously marking the nascent chain for elimination. Here we review the ribosomal stalling and rescue steps upstream of the RQCc, where one witnesses intersection with cellular machineries implicated in translation elongation, translation termination, ribosomal subunit recycling, and mRNA quality control. We emphasize both recent progress and future directions in this area, as well as examples linking ribosomal rescue with the production of Ltn1-RQCc substrates.

    更新日期:2017-10-24
  • Rethinking m6A Readers, Writers, and Erasers
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Kate D. Meyer, Samie R. Jaffrey

    In recent years, m6A has emerged as an abundant and dynamically regulated modification throughout the transcriptome. Recent technological advances have enabled the transcriptome-wide identification of m6A residues, which in turn has provided important insights into the biology and regulation of this pervasive regulatory mark. Also central to our current understanding of m6A are the discovery and characterization of m6A readers, writers, and erasers. Over the last few years, studies into the function of these proteins have led to important discoveries about the regulation and function of m6A. However, during this time our understanding of these proteins has also evolved considerably, sometimes leading to the reversal of early concepts regarding the reading, writing and erasing of m6A. In this review, we summarize recent advances in m6A research, and we highlight how these new findings have reshaped our understanding of how m6A is regulated in the transcriptome.

    更新日期:2017-10-24
  • The Inherent Asymmetry of DNA Replication
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Jonathan Snedeker, Matthew Wooten, Xin Chen

    Semiconservative DNA replication has provided an elegant solution to the fundamental problem of how life is able to proliferate in a way that allows cells, organisms, and populations to survive and replicate many times over. Somewhat lost, however, in our admiration for this mechanism is an appreciation for the asymmetries that occur in the process of DNA replication. As we discuss in this review, these asymmetries arise as a consequence of the structure of the DNA molecule and the enzymatic mechanism of DNA synthesis. Increasing evidence suggests that asymmetries in DNA replication are able to play a central role in the processes of adaptation and evolution by shaping the mutagenic landscape of cells. Additionally, in eukaryotes, recent work has demonstrated that the inherent asymmetries in DNA replication may play an important role in the process of chromatin replication. As chromatin plays an essential role in defining cell identity, asymmetries generated during the process of DNA replication may play critical roles in cell fate decisions related to patterning and development.

    更新日期:2017-10-24
  • The Three-Dimensional Organization of Mammalian Genomes
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Miao Yu, Bing Ren

    Animal development depends on not only the linear genome sequence that embeds millions of cis-regulatory elements, but also the three-dimensional (3D) chromatin architecture that orchestrates the interplay between cis-regulatory elements and their target genes. Compared to our knowledge of the cis-regulatory sequences, the understanding of the 3D genome organization in human and other eukaryotes is still limited. Recent advances in technologies to map the 3D genome architecture have greatly accelerated the pace of discovery. Here, we review emerging concepts of chromatin organization in mammalian cells, discuss the dynamics of chromatin conformation during development, and highlight important roles for chromatin organization in cancer and other human diseases.

    更新日期:2017-10-24
  • Unconventional Roles of Opsins
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Nicole Y. Leung, Craig Montell

    Rhodopsin is the classical light sensor. Although rhodopsin has long been known to be important for image formation in the eye, the requirements for opsins in non–image formation and in extraocular light sensation were revealed much later. Most recent is the demonstration that an opsin in the fruit fly, Drosophila melanogaster, is expressed in pacemaker neurons in the brain and functions in light entrainment of circadian rhythms. However, the biggest surprise is that opsins have light-independent roles, countering more than a century of dogma that they function exclusively as light sensors. Through studies in Drosophila, light-independent roles of opsins have emerged in temperature sensation and hearing. Although these findings have been uncovered in the fruit fly, there are hints that opsins have light-independent roles in a wide array of animals, including mammals. Thus, despite the decades of focus on opsins as light detectors, they represent an important new class of polymodal sensory receptor.

    更新日期:2017-10-24
  • Temporal Patterning in the Drosophila CNS
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Chris Q. Doe

    A small pool of neural progenitors generates the vast diversity of cell types in the CNS. Spatial patterning specifies progenitor identity, followed by temporal patterning within progenitor lineages to expand neural diversity. Recent work has shown that in Drosophila, all neural progenitors (neuroblasts) sequentially express temporal transcription factors (TTFs) that generate molecular and cellular diversity. Embryonic neuroblasts use a lineage-intrinsic cascade of five TTFs that switch nearly every neuroblast cell division; larval optic lobe neuroblasts also use a rapid cascade of five TTFs, but the factors are completely different. In contrast, larval central brain neuroblasts undergo a major molecular transition midway through larval life, and this transition is regulated by a lineage-extrinsic cue (ecdysone hormone signaling). Overall, every neuroblast lineage uses a TTF cascade to generate diversity, illustrating the widespread importance of temporal patterning.

    更新日期:2017-10-24
  • Lessons from Interspecies Mammalian Chimeras
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Fabian Suchy, Hiromitsu Nakauchi

    As chimeras transform from beasts of Greek mythology into tools of contemporary bioscience, secrets of developmental biology and evolutionary divergence are being revealed. Recent advances in stem cell biology and interspecies chimerism have generated new models with extensive basic and translational applications, including generation of transplantable, patient-specific organs.

    更新日期:2017-10-24
  • Cell Sheet Morphogenesis: Dorsal Closure in Drosophila melanogaster as a Model System
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Daniel P. Kiehart, Janice M. Crawford, Andreas Aristotelous, Stephanos Venakides, Glenn S. Edwards

    Dorsal closure is a key process during Drosophila morphogenesis that models cell sheet movements in chordates, including neural tube closure, palate formation, and wound healing. Closure occurs midway through embryogenesis and entails circumferential elongation of lateral epidermal cell sheets that close a dorsal hole filled with amnioserosa cells. Signaling pathways regulate the function of cellular structures and processes, including Actomyosin and microtubule cytoskeletons, cell-cell/cell-matrix adhesion complexes, and endocytosis/vesicle trafficking. These orchestrate complex shape changes and movements that entail interactions between five distinct cell types. Genetic and laser perturbation studies establish that closure is robust, resilient, and the consequence of redundancy that contributes to four distinct biophysical processes: contraction of the amnioserosa, contraction of supracellular Actomyosin cables, elongation (stretching?) of the lateral epidermis, and zipping together of two converging cell sheets. What triggers closure and what the emergent properties are that give rise to its extraordinary resilience and fidelity remain key, extant questions.

    更新日期:2017-10-24
  • Sending and Receiving Hedgehog Signals
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Kostadin Petrov, Bradley M. Wierbowski, Adrian Salic

    Communication between cells pervades the development and physiology of metazoans. In animals, this process is carried out by a relatively small number of signaling pathways, each consisting of a chain of biochemical events through which extracellular stimuli control the behavior of target cells. One such signaling system is the Hedgehog pathway, which is crucial in embryogenesis and is implicated in many birth defects and cancers. Although Hedgehog pathway components were identified by genetic analysis more than a decade ago, our understanding of the molecular mechanisms of signaling is far from complete. In this review, we focus on the biochemistry and cell biology of the Hedgehog pathway. We examine the unique biosynthesis of the Hedgehog ligand, its specialized release from cells into extracellular space, and the poorly understood mechanisms involved in ligand reception and pathway activation at the surface of target cells. We highlight several critical questions that remain open.

    更新日期:2017-10-24
  • Cell Removal: Efferocytosis
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Peter M. Henson

    In metazoans, removal of cells in situ is involved in larval maturation, metamorphosis, and embryonic development. In adults, such cell removal plays a role in the homeostatic maintenance of cell numbers and tissue integrity as well as in the response to cell injury and damage. This removal involves uptake of the whole or fragmented target cells into phagocytes. Depending on the organism, these latter may be near-neighbor tissue cells and/or professional phagocytes such as, in vertebrates, members of the myeloid family of cells, especially macrophages. The uptake processes appear to involve specialized and highly conserved recognition ligands and receptors, intracellular signaling in the phagocytes, and mechanisms for ingestion. The recognition of cells destined for this form of removal is critical and, significantly, is distinguished for the most part from the recognition of foreign materials and organisms by the innate and adaptive immune systems. In keeping with the key role of cell removal in maintaining tissue homeostasis, constant cell removal is normally silent, i.e., does not initiate a local tissue reaction. This article discusses these complex and wide-ranging processes in general terms as well as the implications when these processes are disrupted in inflammation, immunity, and disease.

    更新日期:2017-10-24
  • Excitable Signal Transduction Networks in Directed Cell Migration
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Peter N. Devreotes, Sayak Bhattacharya, Marc Edwards, Pablo A. Iglesias, Thomas Lampert, Yuchuan Miao

    Although directed migration of eukaryotic cells may have evolved to escape nutrient depletion, it has been adopted for an extensive range of physiological events during development and in the adult organism. The subversion of these movements results in disease, such as cancer. Mechanisms of propulsion and sensing are extremely diverse, but most eukaryotic cells move by extending actin-filled protrusions termed macropinosomes, pseudopodia, or lamellipodia or by extension of blebs. In addition to motility, directed migration involves polarity and directional sensing. The hundreds of gene products involved in these processes are organized into networks of parallel and interconnected pathways. Many of these components are activated or inhibited coordinately with stimulation and on each spontaneously extended protrusion. Moreover, these networks display hallmarks of excitability, including all-or-nothing responsiveness and wave propagation. Cellular protrusions result from signal transduction waves that propagate outwardly from an origin and drive cytoskeletal activity. The range of the propagating waves and hence the size of the protrusions can be altered by lowering or raising the threshold for network activation, with larger and wider protrusions favoring gliding or oscillatory behavior over amoeboid migration. Here, we evaluate the variety of models of excitable networks controlling directed migration and outline critical tests. We also discuss the utility of this emerging view in producing cell migration and in integrating the various extrinsic cues that direct migration.

    更新日期:2017-10-24
  • Cell Polarity in Yeast
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Jian-geng Chiou, Mohan K. Balasubramanian, Daniel J. Lew

    A conserved molecular machinery centered on the Cdc42 GTPase regulates cell polarity in diverse organisms. Here we review findings from budding and fission yeasts that reveal both a conserved core polarity circuit and several adaptations that each organism exploits to fulfill the needs of its lifestyle. The core circuit involves positive feedback by local activation of Cdc42 to generate a cluster of concentrated GTP-Cdc42 at the membrane. Species-specific pathways regulate the timing of polarization during the cell cycle, as well as the location and number of polarity sites.

    更新日期:2017-10-24
  • Microtubule-Organizing Centers
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Jingchao Wu, Anna Akhmanova

    The organization of microtubule networks is crucial for controlling chromosome segregation during cell division, for positioning and transport of different organelles, and for cell polarity and morphogenesis. The geometry of microtubule arrays strongly depends on the localization and activity of the sites where microtubules are nucleated and where their minus ends are anchored. Such sites are often clustered into structures known as microtubule-organizing centers, which include the centrosomes in animals and spindle pole bodies in fungi. In addition, other microtubules, as well as membrane compartments such as the cell nucleus, the Golgi apparatus, and the cell cortex, can nucleate, stabilize, and tether microtubule minus ends. These activities depend on microtubule-nucleating factors, such as γ-tubulin-containing complexes and their activators and receptors, and microtubule minus end–stabilizing proteins with their binding partners. Here, we provide an overview of the current knowledge on how such factors work together to control microtubule organization in different systems.

    更新日期:2017-10-24
  • Assessing the Contributions of Motor Enzymes and Microtubule Dynamics to Mitotic Chromosome Motions
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    J. Richard McIntosh

    During my graduate work with Keith Porter, I became fascinated by the mitotic spindle, an interest that has motivated much of my scientific work ever since. I began spindle studies by using electron microscopes, instruments that have made significant contributions to our understanding of spindle organization. Such instruments have helped to elucidate the distributions of spindle microtubules, the interactions among them, their molecular polarity, and their associations with both kinetochores and spindle poles. Our lab has also investigated some processes of spindle physiology: microtubule dynamics, the actions of microtubule-associated proteins (including motor enzymes), the character of forces generated by specific spindle components, and factors that control mitotic progression. Here, I give a personal perspective on some of this intellectual history and on what recent discoveries imply about the mechanisms of chromosome motion.

    更新日期:2017-10-24
  • Centriole Biogenesis: From Identifying the Characters to Understanding the Plot
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Niccolò Banterle, Pierre Gönczy

    The centriole is a beautiful microtubule-based organelle that is critical for the proper execution of many fundamental cellular processes, including polarity, motility, and division. Centriole biogenesis, the making of this miniature architectural wonder, has emerged as an exemplary model to dissect the mechanisms governing the assembly of a eukaryotic organelle. Centriole biogenesis relies on a set of core proteins whose contributions to the assembly process have begun to be elucidated. Here, we review current knowledge regarding the mechanisms by which these core characters function in an orderly fashion to assemble the centriole. In particular, we discuss how having the correct proteins at the right place and at the right time is critical to first scaffold, then initiate, and finally execute the centriole assembly process, thus underscoring fundamental principles governing organelle biogenesis.

    更新日期:2017-10-24
  • Sex and Gender Differences in the Outcomes of Vaccination over the Life Course
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Katie L. Flanagan, Ashley L. Fink, Magdalena Plebanski, Sabra L. Klein

    Both sex (i.e., biological differences) and gender (i.e., social or cultural influences) impact vaccine acceptance, responses, and outcomes. Clinical data illustrate that among children, young adults, and aged individuals, males and females differ in vaccine-induced immune responses, adverse events, and protection. Although males are more likely to receive vaccines, following vaccination, females typically develop higher antibody responses and report more adverse effects of vaccination than do males. Human, nonhuman animal, and in vitro studies reveal numerous immunological, genetic, hormonal, and environmental factors that differ between males and females and contribute to sex- and gender-specific vaccine responses and outcomes. Herein, we address the impact of sex and gender variables that should be considered in preclinical and clinical studies of vaccines.

    更新日期:2017-10-07
  • Proteostatic Tactics in the Strategy of Sterol Regulation
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Margaret A. Wangeline, Nidhi Vashistha, Randolph Y. Hampton

    In eukaryotes, the synthesis and uptake of sterols undergo stringent multivalent regulation. Both individual enzymes and transcriptional networks are controlled to meet changing needs of the many sterol pathway products. Regulation is tailored by evolution to match regulatory constraints, which can be very different in distinct species. Nevertheless, a broadly conserved feature of many aspects of sterol regulation is employment of proteostasis mechanisms to bring about control of individual proteins. Proteostasis is the set of processes that maintain homeostasis of a dynamic proteome. Proteostasis includes protein quality control pathways for the detection, and then the correction or destruction, of the many misfolded proteins that arise as an unavoidable feature of protein-based life. Protein quality control displays not only the remarkable breadth needed to manage the wide variety of client molecules, but also extreme specificity toward the misfolded variants of a given protein. These features are amenable to evolutionary usurpation as a means to regulate proteins, and this approach has been used in sterol regulation. We describe both well-trod and less familiar versions of the interface between proteostasis and sterol regulation and suggest some underlying ideas with broad biological and clinical applicability.

    更新日期:2017-10-07
  • Coping with Protein Quality Control Failure
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Esther Pilla, Kim Schneider, Anne Bertolotti

    Cells and organisms have evolved numerous mechanisms to cope with and to adapt to unexpected challenges and harsh conditions. Proteins are essential to perform the vast majority of cellular and organismal functions. To maintain a healthy proteome, cells rely on a network of factors and pathways collectively known as protein quality control (PQC) systems, which not only ensure that newly synthesized proteins reach a functional conformation but also are essential for surveillance, prevention, and rescue of protein defects. The main players of PQC systems are chaperones and protein degradation systems: the ubiquitin-proteasome system and autophagy. Here we provide an integrated overview of the diverse PQC systems in eukaryotic cells in health and diseases, with an emphasis on the key regulatory aspects and their cross talks. We also highlight how PQC regulation may be exploited for potential therapeutic benefit.

    更新日期:2017-10-07
  • Mechanisms of Tail-Anchored Membrane Protein Targeting and Insertion
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Un Seng Chio, Hyunju Cho, Shu-ou Shan

    Proper localization of membrane proteins is essential for the function of biological membranes and for the establishment of organelle identity within a cell. Molecular machineries that mediate membrane protein biogenesis need to not only achieve a high degree of efficiency and accuracy, but also prevent off-pathway aggregation events that can be detrimental to cells. The posttranslational targeting of tail-anchored proteins (TAs) provides tractable model systems to probe these fundamental issues. Recent advances in understanding TA-targeting pathways reveal sophisticated molecular machineries that drive and regulate these processes. These findings also suggest how an interconnected network of targeting factors, cochaperones, and quality control machineries together ensures robust membrane protein biogenesis.

    更新日期:2017-10-07
  • Temporal Patterning in the Drosophila CNS
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Chris Q. Doe

    A small pool of neural progenitors generates the vast diversity of cell types in the CNS. Spatial patterning specifies progenitor identity, followed by temporal patterning within progenitor lineages to expand neural diversity. Recent work has shown that in Drosophila, all neural progenitors (neuroblasts) sequentially express temporal transcription factors (TTFs) that generate molecular and cellular diversity. Embryonic neuroblasts use a lineage-intrinsic cascade of five TTFs that switch nearly every neuroblast cell division; larval optic lobe neuroblasts also use a rapid cascade of five TTFs, but the factors are completely different. In contrast, larval central brain neuroblasts undergo a major molecular transition midway through larval life, and this transition is regulated by a lineage-extrinsic cue (ecdysone hormone signaling). Overall, every neuroblast lineage uses a TTF cascade to generate diversity, illustrating the widespread importance of temporal patterning.

    更新日期:2017-10-07
  • Cell Sheet Morphogenesis: Dorsal Closure in Drosophila melanogaster as a Model System
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    Daniel P. Kiehart, Janice M. Crawford, Andreas Aristotelous, Stephanos Venakides, Glenn S. Edwards

    Dorsal closure is a key process during Drosophila morphogenesis that models cell sheet movements in chordates, including neural tube closure, palate formation, and wound healing. Closure occurs midway through embryogenesis and entails circumferential elongation of lateral epidermal cell sheets that close a dorsal hole filled with amnioserosa cells. Signaling pathways regulate the function of cellular structures and processes, including Actomyosin and microtubule cytoskeletons, cell-cell/cell-matrix adhesion complexes, and endocytosis/vesicle trafficking. These orchestrate complex shape changes and movements that entail interactions between five distinct cell types. Genetic and laser perturbation studies establish that closure is robust, resilient, and the consequence of redundancy that contributes to four distinct biophysical processes: contraction of the amnioserosa, contraction of supracellular Actomyosin cables, elongation (stretching?) of the lateral epidermis, and zipping together of two converging cell sheets. What triggers closure and what the emergent properties are that give rise to its extraordinary resilience and fidelity remain key, extant questions.

    更新日期:2017-10-07
  • Assessing the Contributions of Motor Enzymes and Microtubule Dynamics to Mitotic Chromosome Motions
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2017-10-06
    J. Richard McIntosh

    During my graduate work with Keith Porter, I became fascinated by the mitotic spindle, an interest that has motivated much of my scientific work ever since. I began spindle studies by using electron microscopes, instruments that have made significant contributions to our understanding of spindle organization. Such instruments have helped to elucidate the distributions of spindle microtubules, the interactions among them, their molecular polarity, and their associations with both kinetochores and spindle poles. Our lab has also investigated some processes of spindle physiology: microtubule dynamics, the actions of microtubule-associated proteins (including motor enzymes), the character of forces generated by specific spindle components, and factors that control mitotic progression. Here, I give a personal perspective on some of this intellectual history and on what recent discoveries imply about the mechanisms of chromosome motion.

    更新日期:2017-10-07
  • Chemical Principles in Tissue Clearing and Staining Protocols for Whole-Body Cell Profiling
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Kazuki Tainaka, Akihiro Kuno, Shimpei I. Kubota, Tatzya Murakami, Hiroki R. Ueda

    Mammalian bodies have more than a billion cells per cubic centimeter, which makes whole-body cell (WBC) profiling of an organism one of the ultimate challenges in biology and medicine. Recent advances in tissue-clearing technology have enabled rapid and comprehensive cellular analyses in whole organs and in the whole body by a combination of state-of-the-art technologies of optical imaging and image informatics. In this review, we focus mainly on the chemical principles in currently available techniques for tissue clearing and staining to facilitate our understanding of their underlying mechanisms. Tissue clearing is usually conducted by the following steps: (a) fixation, (b) permeabilization, (c) decolorizing, and (d) refractive index (RI) matching. To phenotype individual cells after tissue clearing, it is important to visualize genetically encoded fluorescent reporters and/or to stain tissues with fluorescent dyes, fluorescent labeled antibodies, or nucleic acid probes. Although some technical challenges remain, the chemical principles in tissue clearing and staining for WBC profiling will enable various applications, such as identifying cellular circuits across multiple organs and measuring their dynamics in stochastic and proliferative cellular processes, for example, autoimmune and malignant neoplastic diseases.

    更新日期:2017-08-24
  • Emergence and Evolution of Secondary Lymphoid Organs
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Harold R. Neely, Martin F. Flajnik

    For effective adaptive immunity to foreign antigens (Ag), secondary lymphoid organs (SLO) provide the confined environment in which Ag-restricted lymphocytes, with very low precursor frequencies, interact with Ag on Ag-presenting cells (APC). The spleen is the primordial SLO, arising in conjunction with adaptive immunity in early jawed vertebrates. The spleen, especially the spleen's lymphoid compartment, the white pulp (WP), has undergone numerous modifications over evolutionary time. We describe the progressive advancement of splenic WP complexity, which evolved in parallel with the increasing functionality of adaptive immunity. The Ag-presenting function of follicular dendritic cells (FDC) also likely emerged at the inception of adaptive immunity, and we propose that a single type of hematopoietically derived APC displayed Ag to both T and B cells. A dedicated FDC, derived from a vascular precursor, is a recent evolutionary innovation that likely permitted the robust affinity maturation found in mammals.

    更新日期:2017-08-24
  • Lymphangiogenesis: Origin, Specification, and Cell Fate Determination
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Noelia Escobedo, Guillermo Oliver

    The two vascular systems of our body are the blood and the lymphatic vasculature. Our understanding of the genes and molecular mechanisms controlling the development of the lymphatic vasculature network has significantly improved. The availability of novel animal models and better imaging tools led to the identification of lymphatics in tissues and organs previously thought to be devoid of them. Similarly, the classical textbook list of established functional roles of the lymphatic system has been expanded by the addition of novel findings. In this review we provide a historical perspective of some of the important landmarks that opened the doors to researchers working in this field. We also summarize some of the current views about embryonic lymphangiogenesis, particularly about the source(s), commitment, and differentiation of lymphatic endothelial cells.

    更新日期:2017-08-24
  • Regulation of Hematopoiesis and Osteogenesis by Blood Vessel–Derived Signals
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Saravana K. Ramasamy, Anjali P. Kusumbe, Tomer Itkin, Shiri Gur-Cohen, Tsvee Lapidot, Ralf H. Adams

    In addition to their conventional role as a versatile transport system, blood vessels provide signals controlling organ development, regeneration, and stem cell behavior. In the skeletal system, certain capillaries support perivascular osteoprogenitor cells and thereby control bone formation. Blood vessels are also a critical component of niche microenvironments for hematopoietic stem cells. Here we discuss key pathways and factors controlling endothelial cell behavior in bone, the role of vessels in osteogenesis, and the nature of vascular stem cell niches in bone marrow.

    更新日期:2017-08-24
  • Hemodynamic Control of Endothelial Cell Fates in Development
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Guillermo García-Cardeña, Bendix R. Slegtenhorst

    Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system. From the onset of blood flow, the embryonic vasculature is continuously exposed to a variety of hemodynamic forces. These biomechanical stimuli are key determinants of vascular cell specification and remodeling and the establishment of vascular homeostasis. In recent years, major advances have been made in our understanding of mechano-activated signaling networks that control both spatiotemporal and structural aspects of vascular development. It has become apparent that a major site for mechanotransduction is situated at the interface of blood and the vessel wall and that this process is controlled by the vascular endothelium. In this review, we discuss the hemodynamic control of endothelial cell fates, focusing on arterial-venous specification, lymphatic development, and the endothelial-to-hematopoietic transition, and present some recent insights into the mechano-activated pathways driving these cell fate decisions in the developing embryo.

    更新日期:2017-08-24
  • The Role of Adipocytes in Tissue Regeneration and Stem Cell Niches
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Brett Shook, Guillermo Rivera Gonzalez, Sarah Ebmeier, Gabriella Grisotti, Rachel Zwick, Valerie Horsley

    Classically, white adipose tissue (WAT) was considered an inert component of connective tissue but is now appreciated as a major regulator of metabolic physiology and endocrine homeostasis. Recent work defining how WAT develops and expands in vivo emphasizes the importance of specific locations of WAT or depots in metabolic regulation. Interestingly, mature white adipocytes are integrated into several tissues. A new perspective regarding the in vivo regulation and function of WAT in these tissues has highlighted an essential role of adipocytes in tissue homeostasis and regeneration. Finally, there has been significant progress in understanding how mature adipocytes regulate the pathology of several diseases. In this review, we discuss these novel roles of WAT in the homeostasis and regeneration of epithelial, muscle, and immune tissues and how they contribute to the pathology of several disorders.

    更新日期:2017-08-24
  • Structural Perspectives on Axon Guidance
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Elena Seiradake, E. Yvonne Jones, Rüdiger Klein

    Axon guidance relies on a combinatorial code of receptor and ligand interactions that direct adhesive/attractive and repulsive cellular responses. Recent structural data have revealed many of the molecular mechanisms that govern these interactions and enabled the design of sophisticated mutant tools to dissect their biological functions. Here, we discuss the structure/function relationships of four major classes of guidance cues (ephrins, semaphorins, slits, netrins) and examples of morphogens (Wnt, Shh) and of cell adhesion molecules (FLRT). These cell signaling systems rely on specific modes of receptor-ligand binding that are determined by selective binding sites; however, defined structure-encoded receptor promiscuity also enables cross talk between different receptor/ligand families and can also involve extracellular matrix components. A picture emerges in which a multitude of highly context-dependent structural assemblies determines the finely tuned cellular behavior required for nervous system development.

    更新日期:2017-08-24
  • Cellular and Molecular Mechanisms of MT1-MMP-Dependent Cancer Cell Invasion
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Antonio Castro-Castro, Valentina Marchesin, Pedro Monteiro, Catalina Lodillinsky, Carine Rossé, Philippe Chavrier

    Metastasis is responsible for most cancer-associated deaths. Accumulating evidence based on 3D migration models has revealed a diversity of invasive migratory schemes reflecting the plasticity of tumor cells to switch between proteolytic and nonproteolytic modes of invasion. Yet, initial stages of localized regional tumor dissemination require proteolytic remodeling of the extracellular matrix to overcome tissue barriers. Recent data indicate that surface-exposed membrane type 1–matrix metalloproteinase (MT1-MMP), belonging to a group of membrane-anchored MMPs, plays a central role in pericellular matrix degradation during basement membrane and interstitial tissue transmigration programs. In addition, a large body of work indicates that MT1-MMP is targeted to specialized actin-rich cell protrusions termed invadopodia, which are responsible for matrix degradation. This review describes the multistep assembly of actin-based invadopodia in molecular details. Mechanisms underlying MT1-MMP traffic to invadopodia through endocytosis/recycling cycles, which are key to the invasive program of carcinoma cells, are discussed.

    更新日期:2017-08-24
  • Mechanical Control of Epithelial-to-Mesenchymal Transitions in Development and Cancer
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Laralynne Przybyla, Jonathon M. Muncie, Valerie M. Weaver

    Mechanical force modulates development, influences tissue homeostasis, and contributes to disease. Forces sculpt tissue-level behaviors and direct cell fate by engaging mechanoreceptors and by altering organization of the cytoskeleton and actomyosin contractility to stimulate mechanotransduction mechanisms that alter transcription. Nevertheless, how force specifically leverages mechanotransduction pathways to control transcriptional regulation of cell fate remains unclear. Here we review recent findings specifically in the context of epithelial-to-mesenchymal transitions that have revealed conserved mechanisms whereby extracellular force, mediated through cell–extracellular matrix and cell-cell junctional complexes, induces transcriptional reprogramming to alter cell and tissue fate. We focus on the interplay between tissue mechanics and the epithelial-to-mesenchymal transitions that occur during embryonic development and cancer malignancy. We describe the adhesion-linked cellular machinery that mediates mechano-transduction and elaborate on how these force-linked networks stimulate key transcriptional programs that induce an epithelial-to-mesenchymal phenotypic transition, thereby providing an overview of how mechanical signals can be translated into a change in cell fate.

    更新日期:2017-08-24
  • Plasticity of Cell Migration In Vivo and In Silico
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Veronika te Boekhorst, Luigi Preziosi, Peter Friedl

    Cell migration results from stepwise mechanical and chemical interactions between cells and their extracellular environment. Mechanistic principles that determine single-cell and collective migration modes and their interconversions depend upon the polarization, adhesion, deformability, contractility, and proteolytic ability of cells. Cellular determinants of cell migration respond to extracellular cues, including tissue composition, topography, alignment, and tissue-associated growth factors and cytokines. Both cellular determinants and tissue determinants are interdependent; undergo reciprocal adjustment; and jointly impact cell decision making, navigation, and migration outcome in complex environments. We here review the variability, decision making, and adaptation of cell migration approached by live-cell, in vivo, and in silico strategies, with a focus on cell movements in morphogenesis, repair, immune surveillance, and cancer metastasis.

    更新日期:2017-08-24
  • Focal Adhesion–Independent Cell Migration
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Ewa K. Paluch, Irene M. Aspalter, Michael Sixt

    Cell migration is central to a multitude of physiological processes, including embryonic development, immune surveillance, and wound healing, and deregulated migration is key to cancer dissemination. Decades of investigations have uncovered many of the molecular and physical mechanisms underlying cell migration. Together with protrusion extension and cell body retraction, adhesion to the substrate via specific focal adhesion points has long been considered an essential step in cell migration. Although this is true for cells moving on two-dimensional substrates, recent studies have demonstrated that focal adhesions are not required for cells moving in three dimensions, in which confinement is sufficient to maintain a cell in contact with its substrate. Here, we review the investigations that have led to challenging the requirement of specific adhesions for migration, discuss the physical mechanisms proposed for cell body translocation during focal adhesion–independent migration, and highlight the remaining open questions for the future.

    更新日期:2017-08-24
  • Functions and Regulation of Programmed Cell Death in Plant Development
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Anna Daneva, Zhen Gao, Matthias Van Durme, Moritz K. Nowack

    Programmed cell death (PCD) is a collective term for diverse processes causing an actively induced, tightly controlled cellular suicide. PCD has a multitude of functions in the development and health of multicellular organisms. In comparison to intensively studied forms of animal PCD such as apoptosis, our knowledge of the regulation of PCD in plants remains limited. Despite the importance of PCD in plant development and as a response to biotic and abiotic stresses, the complex molecular networks controlling different forms of plant PCD are only just beginning to emerge. With this review, we provide an update on the considerable progress that has been made over the last decade in our understanding of PCD as an inherent part of plant development. We highlight both functions of developmental PCD and central aspects of its molecular regulation.

    更新日期:2017-08-24
  • Cell Competition: Mechanisms and Physiological Roles
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Cristina Clavería, Miguel Torres

    Cell-competitive interactions are widespread in nature and determine the outcome of a vast variety of biological processes. A particular class of competitive interactions takes place when alterations in intrinsic cellular properties are sensed nonautonomously by comparison between neighboring cells, resulting in the selective elimination of one cell population. This type of cell competition was first described four decades ago in developing epithelia of Drosophila. In the last 15 years, further molecular and cellular analyses have provided essential knowledge about the mechanisms, universality, and physiological relevance of cell competition. The two main phenomena triggering cell competition are alterations in cellular metabolic status and alterations in epithelial apico-basal polarity, while other reported pathways are less characterized. Cell competition plays essential roles in quality control, homeostasis, and repair of developing and adult tissues, and depending on the context, it may function as a tumor-suppressing or tumor-promoting mechanism.

    更新日期:2017-08-24
  • Metabolism and the Control of Cell Fate Decisions and Stem Cell Renewal
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Kyoko Ito, Keisuke Ito

    Although the stem cells of various tissues remain in the quiescent state to maintain their undifferentiated state, they also undergo cell divisions as required, and if necessary, even a single stem cell is able to provide for lifelong tissue homeostasis. Stem cell populations are precisely controlled by the balance between their symmetric and asymmetric divisions, with their division patterns determined by whether the daughter cells involved retain their self-renewal capacities. Recent studies have reported that metabolic pathways and the distribution of mitochondria are regulators of the division balance of stem cells and that metabolic defects can shift division balance toward symmetric commitment, which leads to stem cell exhaustion. It has also been observed that in asymmetric division, old mitochondria, which are central metabolic organelles, are segregated to the daughter cell fated to cell differentiation, whereas in symmetric division, young and old mitochondria are equally distributed between both daughter cells. Thus, metabolism and mitochondrial biology play important roles in stem cell fate decisions. As these decisions directly affect tissue homeostasis, understanding their regulatory mechanisms in the context of cellular metabolism is critical.

    更新日期:2017-08-24
  • How Bacteria Subvert Animal Cell Structure and Function
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Alyssa Jimenez, Didi Chen, Neal M. Alto

    Bacterial pathogens encode a wide variety of effectors and toxins that hijack host cell structure and function. Of particular importance are virulence factors that target actin cytoskeleton dynamics critical for cell shape, stability, motility, phagocytosis, and division. In addition, many bacteria target organelles of the general secretory pathway (e.g., the endoplasmic reticulum and the Golgi complex) and recycling pathways (e.g., the endolysosomal system) to establish and maintain an intracellular replicative niche. Recent research on the biochemistry and structural biology of bacterial effector proteins and toxins has begun to shed light on the molecular underpinnings of these host-pathogen interactions. This exciting work is revealing how pathogens gain control of the complex and dynamic host cellular environments, which impacts our understanding of microbial infectious disease, immunology, and human cell biology.

    更新日期:2017-08-24
  • The Cytoophidium and Its Kind: Filamentation and Compartmentation of Metabolic Enzymes
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Ji-Long Liu

    Compartmentation is essential for the localization of biological processes within a cell. In 2010, three groups independently reported that cytidine triphosphate synthase (CTPS), a metabolic enzyme for de novo synthesis of the nucleotide CTP, is compartmentalized in cytoophidia (Greek for “cellular snakes”) in bacteria, yeast, and fruit flies. Subsequent studies demonstrate that CTPS can also form filaments in human cells. Thus, the cytoophidium represents a new type of intracellular compartment that is strikingly conserved across prokaryotes and eukaryotes. Multiple lines of evidence have recently suggested that polymerization of metabolic enzymes such as CTPS and inosine monophosphate dehydrogenase into filamentous cytoophidia modulates enzymatic activity. With many more metabolic enzymes found to form the cytoophidium and its kind, compartmentation via filamentation may serve as a general mechanism for the regulation of metabolism.

    更新日期:2017-08-24
  • TCR Signal Strength and T Cell Development
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Nicholas R.J. Gascoigne, Vasily Rybakin, Oreste Acuto, Joanna Brzostek

    Thymocyte selection involves the positive and negative selection of the repertoire of T cell receptors (TCRs) such that the organism does not suffer autoimmunity, yet has the benefit of the ability to recognize any invading pathogen. The signal transduced through the TCR is translated into a number of different signaling cascades that result in transcription factor activity in the nucleus and changes to the cytoskeleton and motility. Negative selection involves inducing apoptosis in thymocytes that express strongly self-reactive TCRs, whereas positive selection must induce survival and differentiation programs in cells that are more weakly self-reactive. The TCR recognition event is analog by nature, but the outcome of signaling is not. A large number of molecules regulate the strength of the TCR-derived signal at various points in the cascades. This review discusses the various factors that can regulate the strength of the TCR signal during thymocyte development.

    更新日期:2017-08-24
  • Signaling and Polarized Communication Across the T Cell Immunological Synapse
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Michael L. Dustin, Kaushik Choudhuri

    T cells express a somatically recombined antigen receptor (αβTCR) that is calibrated during development to respond to changes in peptides displayed by major histocompatibility complex proteins (pMHC) on the surface of antigen-presenting cells (APC). A key characteristic of pMHC for adaptive immunity is the ability to sample internal states of cells and tissues to sensitively detect changes associated with infection, cell derangement, or tissue injury. Physical T cell–APC contact sets up an axis for polarization of TCR, adhesion molecules, kinases, cytoskeletal elements, and organelles inherent in this mode of juxtacrine signaling. The discovery of further lateral organization of the TCR and adhesion molecules into radially symmetric compartments, the immunological synapse, revealed an intersecting plane of symmetry and potential for regulated symmetry breaking to control duration of T cell–APC interactions. In addition to organizing signaling machinery, the immunological synapse directs the polarized transport and secretion of cytokines and cytolytic agents across the synaptic cleft and is a site for the generation and exocytic release of bioactive microvesicles that can functionally affect recipient APC and other cells in the environment. This machinery is coopted by retroviruses, and human immune deficiency virus-1 may even use antigen-specific synapses for infection of healthy T cells. Here, we discuss recent advances in the molecular and cell biological mechanisms of immunological synapse assembly and signaling and its role in intercellular communication across the synaptic cleft.

    更新日期:2017-08-24
  • Endoplasmic Reticulum–Plasma Membrane Associations: Structures and Functions
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Alessandra Gallo, Christian Vannier, Thierry Galli

    Inside eukaryotic cells, membrane contact sites (MCSs), regions where two membrane-bound organelles are apposed at less than 30 nm, generate regions of important lipid and calcium exchange. This review principally focuses on the structure and the function of MCSs between the endoplasmic reticulum (ER) and the plasma membrane (PM). Here we describe how tethering structures form and maintain these junctions and, in some instances, participate in their function. We then discuss recent insights into the mechanisms by which specific classes of proteins mediate nonvesicular lipid exchange between the ER and PM and how such phenomena, already known to be crucial for maintaining organelle identity, are also emerging as regulators of cell growth and development.

    更新日期:2017-08-24
  • TFEB and TFE3: Linking Lysosomes to Cellular Adaptation to Stress*
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Nina Raben, Rosa Puertollano

    In recent years, our vision of lysosomes has drastically changed. Formerly considered to be mere degradative compartments, they are now recognized as key players in many cellular processes. The ability of lysosomes to respond to different stimuli revealed a complex and coordinated regulation of lysosomal gene expression. This review discusses the participation of the transcription factors TFEB and TFE3 in the regulation of lysosomal function and biogenesis, as well as the role of the lysosomal pathway in cellular adaptation to a variety of stress conditions, including nutrient deprivation, mitochondrial dysfunction, protein misfolding, and pathogen infection. We also describe how cancer cells make use of TFEB and TFE3 to promote their own survival and highlight the potential of these transcription factors as therapeutic targets for the treatment of neurological and lysosomal diseases.

    更新日期:2017-08-24
  • The Lysosome as a Regulatory Hub
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Rushika M. Perera, Roberto Zoncu

    The lysosome has long been viewed as the recycling center of the cell. However, recent discoveries have challenged this simple view and have established a central role of the lysosome in nutrient-dependent signal transduction. The degradative role of the lysosome and its newly discovered signaling functions are not in conflict but rather cooperate extensively to mediate fundamental cellular activities such as nutrient sensing, metabolic adaptation, and quality control of proteins and organelles. Moreover, lysosome-based signaling and degradation are subject to reciprocal regulation. Transcriptional programs of increasing complexity control the biogenesis, composition, and abundance of lysosomes and fine-tune their activity to match the evolving needs of the cell. Alterations in these essential activities are, not surprisingly, central to the pathophysiology of an ever-expanding spectrum of conditions, including storage disorders, neurodegenerative diseases, and cancer. Thus, unraveling the functions of this fascinating organelle will contribute to our understanding of the fundamental logic of metabolic organization and will point to novel therapeutic avenues in several human diseases.

    更新日期:2017-08-24
  • Cargo Capture and Bulk Flow in the Early Secretory Pathway
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Charles Barlowe, Ari Helenius

    Transport of newly synthesized proteins from the endoplasmic reticulum (ER) to the Golgi complex is highly selective. As a general rule, such transport is limited to soluble and membrane-associated secretory proteins that have reached properly folded and assembled conformations. To secure the efficiency, fidelity, and control of this crucial transport step, cells use a combination of mechanisms. The mechanisms are based on selective retention of proteins in the ER to prevent uptake into transport vesicles, on selective capture of proteins in COPII carrier vesicles, on inclusion of proteins in these vesicles by default as part of fluid and membrane bulk flow, and on selective retrieval of proteins from post-ER compartments by retrograde vesicle transport.

    更新日期:2017-08-24
  • Cytoplasmic Streaming in the Drosophila Oocyte
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Margot E. Quinlan

    Objects are commonly moved within the cell by either passive diffusion or active directed transport. A third possibility is advection, in which objects within the cytoplasm are moved with the flow of the cytoplasm. Bulk movement of the cytoplasm, or streaming, as required for advection, is more common in large cells than in small cells. For example, streaming is observed in elongated plant cells and the oocytes of several species. In the Drosophila oocyte, two stages of streaming are observed: relatively slow streaming during mid-oogenesis and streaming that is approximately ten times faster during late oogenesis. These flows are implicated in two processes: polarity establishment and mixing. In this review, I discuss the underlying mechanism of streaming, how slow and fast streaming are differentiated, and what we know about the physiological roles of the two types of streaming.

    更新日期:2017-08-24
  • Phosphoinositides in Control of Membrane Dynamics
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Kay O. Schink, Kia-Wee Tan, Harald Stenmark

    Most functions of eukaryotic cells are controlled by cellular membranes, which are not static entities but undergo frequent budding, fission, fusion, and sculpting reactions collectively referred to as membrane dynamics. Consequently, regulation of membrane dynamics is crucial for cellular functions. A key mechanism in such regulation is the reversible recruitment of cytosolic proteins or protein complexes to specific membranes at specific time points. To a large extent this recruitment is orchestrated by phosphorylated derivatives of the membrane lipid phosphatidylinositol, known as phosphoinositides. The seven phosphoinositides found in nature localize to distinct membrane domains and recruit distinct effectors, thereby contributing strongly to the maintenance of membrane identity. Many of the phosphoinositide effectors are proteins that control membrane dynamics, and in this review we discuss the functions of phosphoinositides in membrane dynamics during exocytosis, endocytosis, autophagy, cell division, cell migration, and epithelial cell polarity, with emphasis on protein effectors that are recruited by specific phosphoinositides during these processes.

    更新日期:2017-08-24
  • Neurogenesis and Gliogenesis in Nervous System Plasticity and Repair
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Jonas Frisén

    The brain constantly changes to store memories and adapt to new conditions. One type of plasticity that has gained increasing interest during the last years is the generation of new cells. The generation of both new neurons and glial cells contributes to neural plasticity and to some neural repair. There are substantial differences between mammalian species with regard to the extent of and mechanisms behind cell exchange in neural plasticity. Both neurogenesis and gliogenesis have several specific features in humans, which may contribute to the unique plasticity of the human brain.

    更新日期:2017-08-24
  • Genotypes, Networks, Phenotypes: Moving Toward Plant Systems Genetics
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Takehiko Ogura, Wolfgang Busch

    One of the central goals in biology is to understand how and how much of the phenotype of an organism is encoded in its genome. Although many genes that are crucial for organismal processes have been identified, much less is known about the genetic bases underlying quantitative phenotypic differences in natural populations. We discuss the fundamental gap between the large body of knowledge generated over the past decades by experimental genetics in the laboratory and what is needed to understand the genotype-to-phenotype problem on a broader scale. We argue that systems genetics, a combination of systems biology and the study of natural variation using quantitative genetics, will help to address this problem. We present major advances in these two mostly disconnected areas that have increased our understanding of the developmental processes of flowering time control and root growth. We conclude by illustrating and discussing the efforts that have been made toward systems genetics specifically in plants.

    更新日期:2017-08-24
  • Transcriptional Control of Developmental Cell Behaviors
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Yelena Bernadskaya, Lionel Christiaen

    Tissue-specific transcription regulators emerged as key developmental control genes, which operate in the context of complex gene regulatory networks (GRNs) to coordinate progressive cell fate specification and tissue morphogenesis. We discuss how GRNs control the individual cell behaviors underlying complex morphogenetic events. Cell behaviors classically range from mesenchymal cell motility to cell shape changes in epithelial sheets. These behaviors emerge from the tissue-specific, multiscale integration of the local activities of universal and pleiotropic effectors, which underlie modular subcellular processes including cytoskeletal dynamics, cell-cell and cell-matrix adhesion, signaling, polarity, and vesicle trafficking. Extrinsic cues and intrinsic cell competence determine the subcellular spatiotemporal patterns of effector activities. GRNs influence most subcellular activities by controlling only a fraction of the effector-coding genes, which we argue is enriched in effectors involved in reading and processing the extrinsic cues to contextualize intrinsic subcellular processes and canalize developmental cell behaviors. The properties of the transcription-cell behavior interface have profound implications for evolution and disease.

    更新日期:2017-08-24
  • Tissue and Organ Initiation in the Plant Embryo: A First Time for Everything
    Annu. Rev. Cell Dev. Biol. (IF 14.917) Pub Date : 2016-10-06
    Joakim Palovaara, Thijs de Zeeuw, Dolf Weijers

    Land plants can grow to tremendous body sizes, yet even the most complex architectures are the result of iterations of the same developmental processes: organ initiation, growth, and pattern formation. A central question in plant biology is how these processes are regulated and coordinated to allow for the formation of ordered, 3D structures. All these elementary processes first occur in early embryogenesis, during which, from a fertilized egg cell, precursors for all major tissues and stem cells are initiated, followed by tissue growth and patterning. Here we discuss recent progress in our understanding of this phase of plant life. We consider the cellular basis for multicellular development in 3D and focus on the genetic regulatory mechanisms that direct specific steps during early embryogenesis.

    更新日期:2017-08-24
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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