Local Biosynthetic Trafficking Of Synaptic Proteins In Neuronal Dendrites
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Local Biosynthetic Trafficking Of Synaptic Proteins In Neuronal Dendrites
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Author : Aaron Benjamin Bowen
language : en
Publisher:
Release Date : 2017
Local Biosynthetic Trafficking Of Synaptic Proteins In Neuronal Dendrites written by Aaron Benjamin Bowen and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017 with categories.
Neurons face the challenge of regulating the abundance, distribution and repertoire of integral membrane proteins on the surface of their immense, architecturally complex dendritic arbors. While the endoplasmic reticulum (ER) supports local translation of secretory cargo in all dendrites, most dendrites lack the Golgi apparatus (GA), an essential organelle for conventional secretory trafficking. Thus, whether secretory cargo is locally trafficked in dendrites through a non-canonical pathway remains a fundamental question. We have defined the trafficking itinerary for key synaptic molecules in dendrites. Following ER exit, the AMPA-type glutamate receptor GluA1 and neuroligin 1 undergo spatially restricted entry into the dendritic secretory pathway and accumulate in recycling endosomes (REs) located in dendrites and spines prior to reaching the plasma membrane. Surprisingly, surface delivery of GluA1 occurred even when GA function was disrupted. Thus, in addition to their canonical role in protein recycling, REs are critical mediators of forward secretory trafficking in neuronal dendrites and spines through a specialized GA-independent trafficking network. While the SNARE machinery that supports biosynthetic trafficking from the GA to the plasma membrane in neurons is not known, the SNAREs that mediate RE exocytosis have been partially defined. Surprisingly, we found that constitutive trafficking of GluA1 through REs does not depend on VAMP2, an R-SNARE with a well-defined role in RE exocytosis. Instead, the clostridial-neurotoxin insensitive SNARE VAMP7 defined a pool of GluA1-containing transport vesicles and was required for their delivery to the plasma membrane. Synaptic stimulation accelerated the delivery of GluA1 from this pool. Interestingly, while this activity-regulated delivery required VAMP2, inhibition of VAMP7 had no effect on activity-induced exocytosis. Thus, VAMP2 and VAMP7 play complementary roles in activity-induced and constitutive delivery of new synaptic proteins. Overall we have identified a novel biosynthetic pathway that involves GA-independent transfer of cargoes to the dendritic RE compartment. Subsequent exocytosis of biosynthetic REs is constitutively maintained by VAMP7, but can be promoted by synaptic activity in a VAMP2-dependent manner. These results provide crucial insight into membrane trafficking processes that could support experience-dependent learning by rapidly delivering locally synthesized proteins to synaptic locations. Ongoing efforts are focused on the development of novel optical approaches to control secretory trafficking that will ultimately expand our capability to dissect the spatial trafficking of cargoes within the dendrite.
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.
Stochastic Processes In Cell Biology
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Author : Paul C. Bressloff
language : en
Publisher: Springer Nature
Release Date : 2022-01-04
Stochastic Processes In Cell Biology written by Paul C. Bressloff and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-01-04 with Mathematics categories.
This book develops the theory of continuous and discrete stochastic processes within the context of cell biology. In the second edition the material has been significantly expanded, particularly within the context of nonequilibrium and self-organizing systems. Given the amount of additional material, the book has been divided into two volumes, with volume I mainly covering molecular processes and volume II focusing on cellular processes. A wide range of biological topics are covered in the new edition, including stochastic ion channels and excitable systems, molecular motors, stochastic gene networks, genetic switches and oscillators, epigenetics, normal and anomalous diffusion in complex cellular environments, stochastically-gated diffusion, active intracellular transport, signal transduction, cell sensing, bacterial chemotaxis, intracellular pattern formation, cell polarization, cell mechanics, biological polymers and membranes, nuclear structure and dynamics, biological condensates, molecular aggregation and nucleation, cellular length control, cell mitosis, cell motility, cell adhesion, cytoneme-based morphogenesis, bacterial growth, and quorum sensing. The book also provides a pedagogical introduction to the theory of stochastic and nonequilibrium processes – Fokker Planck equations, stochastic differential equations, stochastic calculus, master equations and jump Markov processes, birth-death processes, Poisson processes, first passage time problems, stochastic hybrid systems, queuing and renewal theory, narrow capture and escape, extreme statistics, search processes and stochastic resetting, exclusion processes, WKB methods, large deviation theory, path integrals, martingales and branching processes, numerical methods, linear response theory, phase separation, fluctuation-dissipation theorems, age-structured models, and statistical field theory. This text is primarily aimed at graduate students and researchers working in mathematical biology, statistical and biological physicists, and applied mathematicians interested in stochastic modeling. Applied probabilists should also find it of interest. It provides significant background material in applied mathematics and statistical physics, and introduces concepts in stochastic and nonequilibrium processes via motivating biological applications. The book is highly illustrated and contains a large number of examples and exercises that further develop the models and ideas in the body of the text. It is based on a course that the author has taught at the University of Utah for many years.
Biology Of The Nmda Receptor
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Author : Antonius M. VanDongen
language : en
Publisher: CRC Press
Release Date : 2008-10-29
Biology Of The Nmda Receptor written by Antonius M. VanDongen and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-10-29 with Medical categories.
The NMDA receptor plays a critical role in the development of the central nervous system and in adult neuroplasticity, learning, and memory. Therefore, it is not surprising that this receptor has been widely studied. However, despite the importance of rhythms for the sustenance of life, this aspect of NMDAR function remains poorly studied. Written
Protein Trafficking In Neurons
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Author : Andrew J. Bean
language : en
Publisher: Elsevier
Release Date : 2006-10-27
Protein Trafficking In Neurons written by Andrew J. Bean and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2006-10-27 with Science categories.
The efficient delivery of cellular constituents to their proper location is of fundamental importance for all cells and is of particular interest to neuroscientists, because of the unique functions and complex architecture of neurons. Protein Trafficking in Neurons examines mechanisms of protein trafficking and the role of trafficking in neuronal functioning from development to plasticity to disease. The book is divided into seven sections that review mechanisms of protein transport, the role of protein trafficking in synapse formation, exo- and endocytosis, transport of receptors, trafficking of ion channels and transporters, comparison of trafficking mechanisms in neuronal vs. non-neuronal cell types, and the relationship between trafficking and neuronal diseases such as Alzheimer's, Huntington's and Prion Diseases. Provides a comprehensive examination of membrane/protein movement in neuronal function Sections on synapse development, synaptic transmission, and the role of trafficking in neurological disease Includes a focus on Molecular Mechanisms Illustrated with color summary pictures The only book examining protein trafficking and its functional implications, written by leaders in the field
Golgi Pathology In Neurodegenerative Diseases
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Author : Catherine Rabouille
language : en
Publisher: Frontiers Media SA
Release Date : 2016-03-09
Golgi Pathology In Neurodegenerative Diseases written by Catherine Rabouille and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-03-09 with Neurosciences. Biological psychiatry. Neuropsychiatry categories.
The Golgi apparatus is a central organelle that lies at the heart of the secretory pathway. It ensures post-translational protein modifications such as glycosylation and cleavage as well as protein sorting to neuronal axons and dendrites. Structural and functional alterations of the Golgi apparatus (fragmentation and atrophy), which are collectively termed Golgi pathology, are now recognized as a constant feature of many neuro-degenerative diseases. However, the molecular mechanisms underlying these changes and their precise relevance to neurodegeneration have not yet been completely elucidated. This eBook contains 13 reviews that address the molecular mechanisms of Golgi pathology in Parkinson and Alzheimer diseases, amyotrophic lateral sclerosis (ALS) and spinal muscular atrophies, and discuss their potential relevance to the pathological loss of neuronal cell bodies, axons and synapses.
Biochemical Ecotoxicology
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Author : Francois Gagne
language : en
Publisher: Elsevier
Release Date : 2014-07-07
Biochemical Ecotoxicology written by Francois Gagne and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-07-07 with Medical categories.
Biochemical Ecotoxicology: Principles and Methods presents practical approaches to biochemical ecotoxicology experiments for environmental protection and conservation. With its methodical, stepped approach this essential reference introduces readers to current techniques for toxicity endpoint testing, suitable for laboratories of any size and budget. Each chapter presents a state-of-the-art principle, a quick and inexpensive procedure (including appropriate reagents), case studies, and demonstrations on how to analyze your results. Generic techniques are covered, suitable for a variety of organisms, as well as high-throughput techniques like quantitative polymerase chain reactions and enzyme-linked immunoassays. Cutting-edge approaches, including gPCR arrays and lipidomic techniques, are also included, making this is an essential reference for anyone who needs to assess environmental toxicity. Practical, cost-effective approaches to assess environmental toxicity endpoints for all types of organism Presents theory, methods, case studies and information on how to analyze results State-of-the-art techniques, such as ‘omics’ approaches to toxicology
Synaptic Tagging And Capture
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Author : Sreedharan Sajikumar
language : en
Publisher: Springer
Release Date : 2014-10-15
Synaptic Tagging And Capture written by Sreedharan Sajikumar and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-10-15 with Medical categories.
Serves as a comprehensive introduction and overview of synaptic tagging and capture (STC) and covers the topic from molecular and cellular aspects to behavior. Circa 15 years ago the STC model was proposed to provide a conceptual basis for how short-term memories are transformed into long-term memories. Though the hypothesis remains unconfirmed due to technological limitations, the model is well consolidated and generally accepted in the field. Various researchers have investigated the cellular mechanisms for the formation of long-term memory using the STC model, but this is the first book-length treatments of STC. This volume features an introduction by Prof. Richard Morris and Prof. Cliff Abraham.
Cellular Migration And Formation Of Axons And Dendrites
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Author : Bin Chen
language : en
Publisher: Academic Press
Release Date : 2020-05-29
Cellular Migration And Formation Of Axons And Dendrites written by Bin Chen and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-05-29 with Medical categories.
Cellular Migration and Formation of Neuronal Connections, Second Edition, the latest release in the Comprehensive Developmental Neuroscience series, presents the latest information on the genetic, molecular and cellular mechanisms of neural development. This book provides a much-needed update that underscores the latest research in this rapidly evolving field, with new section editors discussing the technological advances that are enabling the pursuit of new research on brain development. This volume focuses on the formation of axons and dendrites and cellular migration. Features leading experts in various subfields as section editors and article authors Presents articles that have been peer reviewed to ensure accuracy, thoroughness and scholarship Includes coverage of mechanisms which regulate the formation of axons and dendrites and cellular migration Covers neural activity, from cell-intrinsic maturation, to early correlated patterns of activity
Extrasynaptic Gabaa Receptors
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Author : Adam C. Errington
language : en
Publisher: Springer
Release Date : 2014-09-22
Extrasynaptic Gabaa Receptors written by Adam C. Errington and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-09-22 with Medical categories.
GABA is the principal inhibitory neurotransmitter in the CNS and acts via GABAA and GABAB receptors. Recently, a novel form of GABAA receptor-mediated inhibition, termed “tonic” inhibition, has been described. Whereas synaptic GABAA receptors underlie classical “phasic” GABAA receptor-mediated inhibition (inhibitory postsynaptic currents), tonic GABAA receptor-mediated inhibition results from the activation of extrasynaptic receptors by low concentrations of ambient GABA. Extrasynaptic GABAA receptors are composed of receptor subunits that convey biophysical properties ideally suited to the generation of persistent inhibition and are pharmacologically and functionally distinct from their synaptic counterparts. This book highlights ongoing work examining the properties of recombinant and native extrasynaptic GABAA receptors and their preferential targeting by endogenous and clinically relevant agents. In addition, it emphasizes the important role of extrasynaptic GABAA receptors in GABAergic inhibition throughout the CNS and identifies them as a major player in both physiological and pathophysiological processes.