Shaping The Postsynaptic Landscape Understanding The Role Of Neuronal Activity In Local Secretory And Endocytic Protein Trafficking Dynamics
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Shaping The Postsynaptic Landscape Understanding The Role Of Neuronal Activity In Local Secretory And Endocytic Protein Trafficking Dynamics
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Author : Ashley M. Bourke
language : en
Publisher:
Release Date : 2018
Shaping The Postsynaptic Landscape Understanding The Role Of Neuronal Activity In Local Secretory And Endocytic Protein Trafficking Dynamics written by Ashley M. Bourke and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018 with categories.
Neuronal development, morphology, excitability and synapse function rely on the ability to maintain and dynamically regulate the repertoire of channel, receptor and adhesion integral membrane proteins presented on the cell surface with extraordinary spatiotemporal specificity. The requirement for the exact spatiotemporal control of surface protein abundance and spatial distribution is an especially tall order for neuronal cells given their immense size, intricate morphology and segregated domain structure. Precise regulation of biosynthetic and endocytic protein trafficking is further confounded by synaptic activity, and the polarization of the somatic Golgi apparatus (GA) presents an arduous undertaking by newly synthesized dendritic integral membrane proteins. How are these challenges reconciled with space- and time-sensitive protein movements to effectively sustain neuronal function? Where, when and how key synaptic receptor proteins are trafficked to and within remote dendritic domains to meet the exigent demands of the cell have remained fundamental yet challenging questions in neuronal cell biology. Recent findings from the Kennedy lab and others propose the existence of a compartmentalized secretory trafficking network in dendrites yet experimentally investigating the relevance of local vs. centralized trafficking pathways has been impossible because currently there is no way to selectively control forward secretory trafficking from distinct subcellular domains. Here I describe the development and implementation of an opto/chemogenetic approach that allows for local, light-triggered forward trafficking of endoplasmic reticulum (ER)-sequestered proteins from user-defined regions within the cell (e.g. the neuronal cell body vs. individual dendritic branches). We discovered that proteins originating in the cell body could be transported deep into dendrites before surface insertion, with distinct cargoes displaying strikingly different kinetics, spatial distributions and activity dependencies. Surprisingly, proteins entering the dendritic secretory pathway were rapidly dispersed before reaching the surface. Additionally, we discovered that select cargoes are rapidly inserted in the plasma membrane at the axon initial segment (AIS), demonstrating a previously unappreciated role of the AIS as a major forward trafficking hub even for somatodendritic cargoes. Finally, we demonstrate that activity may have opposite effects on subcellular targeting of cargoes processed through somatic and dendritic networks. Our results provide the first quantitative characterization of compartmentalized secretory trafficking, placing important experimental constraints on current models for long-range and local protein trafficking. Once newly delivered synaptic proteins arrive at their functional destinations on the dendritic spine PM, their abundance and spatial distribution can be maintained or drastically modified through their endocytic trafficking depending on the current activity state of the synapse. We hypothesized that local alterations to synapses are mediated in part by regulated trafficking of postsynaptic proteins through organelles called recycling endosomes (REs), which act as reservoirs for important postsynaptic molecules. REs are housed within a large fraction of dendritic spines, the major postsynaptic sites of excitatory neurotransmission, and are thus well-poised to rapidly respond to changes in local activity to modulate synaptic structure and function. Using optical techniques coupled with local synapse activation and inactivation, we discovered that the rate of constitutive cargo flux through REs bidirectionally scales with synaptic activity at individual synaptic sites. Additionally, we demonstrate that RE cargo trafficking is coupled to synaptic activity by NMDA receptors and extracellular calcium. Finally, we demonstrate the synapse-specific, activity-dependent internalization of AMPA-type glutamate receptor 1 (GluA1), a key synaptic protein and known RE cargo. Overall, we have developed a novel optical approach for controlling secretory trafficking and we have characterized how neuronal activity influences the spatiotemporal properties of secretory and endocytic protein trafficking within distinct neuronal sub-compartments. These results provide crucial insight into how membrane trafficking processes might establish, maintain and modulate the molecular composition of synapses to support diverse forms of experience-dependent plasticity. Ongoing efforts are focused on both the proteomic mapping of the RE as well as the application of our novel optical approach to control the secretory trafficking of endogenous proteins.
Macromolecular Protein Complexes Iii Structure And Function
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Author : J. Robin Harris
language : en
Publisher: Springer Nature
Release Date : 2020-11-30
Macromolecular Protein Complexes Iii Structure And Function written by J. Robin Harris and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-11-30 with Science categories.
This book covers important topics such as the dynamic structure and function of the 26S proteasome, the DNA replication machine: structure and dynamic function and the structural organization and protein–protein interactions in the human adenovirus capsid, to mention but a few. The 18 chapters included here, written by experts in their specific field, are at the forefront of scientific knowledge. The impressive integration of structural data from X-ray crystallography with that from cryo-electron microscopy is apparent throughout the book. In addition, functional aspects are also given a high priority. Chapter 1 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
Trafficking Inside Cells
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Author : Nava Segev
language : en
Publisher: Springer Science & Business Media
Release Date : 2010-05-30
Trafficking Inside Cells written by Nava Segev and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010-05-30 with Science categories.
This book covers the past, present and future of the intra-cellular trafficking field, which has made a quantum leap in the last few decades. It details how the field has developed and evolved as well as examines future directions.
Huntington S Disease
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Author : Oliver Quarrell
language : en
Publisher: Oxford University Press
Release Date : 2008-02-28
Huntington S Disease written by Oliver Quarrell and has been published by Oxford University Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-02-28 with Family & Relationships categories.
Huntington's disease affects 1 person in 10,000 but this figure is an underestimate because the immediate carer, spouse/partner and the close relatives at risk of developing this condition in the future are also affected. The new edition has been revised to include important new developments that have occurred in the field in recent years.
The Computational Brain 25th Anniversary Edition
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Author : Patricia S. Churchland
language : en
Publisher: MIT Press
Release Date : 2016-11-04
The Computational Brain 25th Anniversary Edition written by Patricia S. Churchland and has been published by MIT Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-11-04 with Science categories.
An anniversary edition of the classic work that influenced a generation of neuroscientists and cognitive neuroscientists. Before The Computational Brain was published in 1992, conceptual frameworks for brain function were based on the behavior of single neurons, applied globally. In The Computational Brain, Patricia Churchland and Terrence Sejnowski developed a different conceptual framework, based on large populations of neurons. They did this by showing that patterns of activities among the units in trained artificial neural network models had properties that resembled those recorded from populations of neurons recorded one at a time. It is one of the first books to bring together computational concepts and behavioral data within a neurobiological framework. Aimed at a broad audience of neuroscientists, computer scientists, cognitive scientists, and philosophers, The Computational Brain is written for both expert and novice. This anniversary edition offers a new preface by the authors that puts the book in the context of current research. This approach influenced a generation of researchers. Even today, when neuroscientists can routinely record from hundreds of neurons using optics rather than electricity, and the 2013 White House BRAIN initiative heralded a new era in innovative neurotechnologies, the main message of The Computational Brain is still relevant.
Dancing Protein Clouds Intrinsically Disordered Proteins In The Norm And Pathology
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Author : Vladimir Uversky
language : en
Publisher: Academic Press
Release Date : 2019-09-15
Dancing Protein Clouds Intrinsically Disordered Proteins In The Norm And Pathology written by Vladimir Uversky and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-09-15 with categories.
"Dancing protein clouds: Intrinsically disordered proteins in the norm and pathology" represents a set of selected studies on a variety of research topics related to intrinsically disordered proteins. Topics in this update include structural and functional characterization of several important intrinsically disordered proteins, such as 14-3-3 proteins and their partners, as well as proteins from muscle sarcomere; representation of intrinsic disorder-related concept of protein structure-function continuum; discussion of the role of intrinsic disorder in phenotypic switching; consideration of the role of intrinsically disordered proteins in the pathogenesis of neurodegenerative diseases and cancer; discussion of the roles of intrinsic disorder in functional amyloids; demonstration of the usefulness of the analysis of translational diffusion of unfolded and intrinsically disordered proteins; consideration of various computational tools for evaluation of functions of intrinsically disordered regions; and discussion of the role of shear stress in the amyloid formation of intrinsically disordered regions in the brain. Provides some recent studies on the intrinsically disordered proteins and their functions, as well as on the involvement of intrinsically disordered proteins in pthogenesis of various diseases Contains numerous illustrative materials (color figures, diagrams, and tables) to help the readers to delve in the information provided Includes contributions from recognized experts in the field
Epigenetics Of Aging
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Author : Trygve O. Tollefsbol
language : en
Publisher: Springer Science & Business Media
Release Date : 2009-11-11
Epigenetics Of Aging written by Trygve O. Tollefsbol and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2009-11-11 with Medical categories.
Recent studies have indicated that epigenetic processes may play a major role in both cellular and organismal aging. These epigenetic processes include not only DNA methylation and histone modifications, but also extend to many other epigenetic mediators such as the polycomb group proteins, chromosomal position effects, and noncoding RNA. The topics of this book range from fundamental changes in DNA methylation in aging to the most recent research on intervention into epigenetic modifications to modulate the aging process. The major topics of epigenetics and aging covered in this book are: 1) DNA methylation and histone modifications in aging; 2) Other epigenetic processes and aging; 3) Impact of epigenetics on aging; 4) Epigenetics of age-related diseases; 5) Epigenetic interventions and aging: and 6) Future directions in epigenetic aging research. The most studied of epigenetic processes, DNA methylation, has been associated with cellular aging and aging of organisms for many years. It is now apparent that both global and gene-specific alterations occur not only in DNA methylation during aging, but also in several histone alterations. Many epigenetic alterations can have an impact on aging processes such as stem cell aging, control of telomerase, modifications of telomeres, and epigenetic drift can impact the aging process as evident in the recent studies of aging monozygotic twins. Numerous age-related diseases are affected by epigenetic mechanisms. For example, recent studies have shown that DNA methylation is altered in Alzheimer’s disease and autoimmunity. Other prevalent diseases that have been associated with age-related epigenetic changes include cancer and diabetes. Paternal age and epigenetic changes appear to have an effect on schizophrenia and epigenetic silencing has been associated with several of the progeroid syndromes of premature aging. Moreover, the impact of dietary or drug intervention into epigenetic processes as they affect normal aging or age-related diseases is becoming increasingly feasible.
Advanced Healthcare Materials
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Author : Ashutosh Tiwari
language : en
Publisher: John Wiley & Sons
Release Date : 2014-05-09
Advanced Healthcare Materials written by Ashutosh Tiwari and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-05-09 with Technology & Engineering categories.
Offers a comprehensive and interdisciplinary view of cutting-edge research on advanced materials for healthcare technology and applications Advanced healthcare materials are attracting strong interest in fundamental as well as applied medical science and technology. This book summarizes the current state of knowledge in the field of advanced materials for functional therapeutics, point-of-care diagnostics, translational materials, and up-and-coming bioengineering devices. Advanced Healthcare Materials highlights the key features that enable the design of stimuli-responsive smart nanoparticles, novel biomaterials, and nano/micro devices for either diagnosis or therapy, or both, called theranostics. It also presents the latest advancements in healthcare materials and medical technology. The senior researchers from global knowledge centers have written topics including: State-of-the-art of biomaterials for human health Micro- and nanoparticles and their application in biosensors The role of immunoassays Stimuli-responsive smart nanoparticles Diagnosis and treatment of cancer Advanced materials for biomedical application and drug delivery Nanoparticles for diagnosis and/or treatment of Alzheimers disease Hierarchical modelling of elastic behavior of human dental tissue Biodegradable porous hydrogels Hydrogels in tissue engineering, drug delivery, and wound care Modified natural zeolites Supramolecular hydrogels based on cyclodextrin poly(pseudo)rotaxane Polyhydroxyalkanoate-based biomaterials Biomimetic molecularly imprinted polymers
Imaging Living Cells
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Author : Rosario Rizzuto
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-12-06
Imaging Living Cells written by Rosario Rizzuto and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-06 with Science categories.
Intended for bench-top use, this lab manual is suitable for both scientists and graduate students, since it combines an update on the most advanced imaging procedures with detailed protocols. Examples, carefully selected from the wide repertoire of cell pyhsiology, cover such different functional aspects as distribution of multiple ions, electrical activity, exo-endocytosis, gene expression, and the cell cycle.
Unconventional Protein Secretion
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Author : Andrea Pompa
language : en
Publisher: Humana
Release Date : 2016-09-24
Unconventional Protein Secretion written by Andrea Pompa and has been published by Humana this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-09-24 with Science categories.
This volume presents relevant background information to understanding the molecular basis governing unconventional protein secretion (UPS), and in particular explores the latest techniques and protocols that have been successfully applied for the study of this topic. Detailed chapters include an overview of conventional and unconventional secretory pathways along with multidisciplinary approaches and methods used for UPS analysis in different organisms. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Unconventional Protein Secretion: Methods and Protocols will be useful for all interested in the secretory pathway field as well as applications in cell biology, cell development, biomedical research, and healthcare.