Biosynthetic Membrane Trafficking Pathways In Neurons
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Biosynthetic Membrane Trafficking Pathways In Neurons
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Author : Michelle Anne Burack
language : en
Publisher:
Release Date : 2003
Biosynthetic Membrane Trafficking Pathways In Neurons written by Michelle Anne Burack and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2003 with categories.
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
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.
Regulation Of Biosynthetic Cargo Trafficking In Neurons
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Author : Iryna Pustova
language : en
Publisher:
Release Date : 2023
Regulation Of Biosynthetic Cargo Trafficking In Neurons written by Iryna Pustova and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2023 with categories.
Neurons are highly polarized cells with extremely long projections: dendrites and axons (together referred to as neurites). The central secretory dogma states that all protein synthesis and early secretory events take place in the cell body of a neuron, the soma. Yet, computational studies fail to reconcile experimental evidence with this notion proposing that there must be local protein synthesis and trafficking routes in distal neurites to support the function of a neuronal cell (reviewed in Chapter 1). Indeed, multiple lines of evidence from transcriptomics and protein translation studies indicate that local protein synthesis takes place independently of the soma. Amongst locally translated proteins, there are numerous secreted and membrane proteins. Yet, it is not clear how these newly synthesized proteins can be secreted locally, mainly, because the secretory pathway is largely understudied, especially in human neurons. Thus, I used human-induced pluripotent stem cells that I differentiated into cortical neurons to study the secretory pathway in distal neurites. In Chapter 2, I show that the secretory events occur in distal neuronal projections independently of the cell body. In fact, I find that nascent proteins are trafficked using an unconventional pathway via recycling endosomes. In addition, I uncover surprising new roles for TFG, a ubiquitously expressed protein and an important player in the early secretory pathway. Missense mutations in TFG have been identified in patients with neurodegenerative disorders though it is not clear how TFG results in disease. In Chapter 2, I show that TFG is not only important in the early secretory events in the conventional ER-to-Golgi trafficking, but it also mediates the unconventional secretory route where newly synthesized proteins exit ER and enter endosomes locally in distal neurites. Curiously, I find that TFG abundantly localizes with endosomes, suggesting that it must have an additional role in the endosomal pathway. Thus, I find that TFG has three distinct roles in neuronal cells: 1) conventional ER-to-Golgi trafficking in the soma, 2) unconventional ER-to-endosome route in distal neurites, 3) regulation of endosomal pathway. Future work, discussed in Chapter 3, will shed light on how TFG regulates the latter and how mutations in TFG lead to neurodegeneration.
Membrane Trafficking And Endocytosis In Neurons
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Author : Ayesha Murshid
language : en
Publisher:
Release Date : 2008
Membrane Trafficking And Endocytosis In Neurons written by Ayesha Murshid and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008 with categories.
"In mammalian cells, two main membrane trafficking pathways, the secretory and endocytic pathways are important for many biological functions. Secretory proteins are synthesized on ribosomes inside the cells, translocated into the ER for proper folding, later mature in the Golgi and continue their journey to the plasma membrane. Endocytosis is defined as a process of vesicle formation from the plasma membrane, where external solutes like nutrients, growth factors and transmembrane proteins are internalized by the cell to endosomal compartments. Internalized protein can either be degraded in lysosomes or recycled back to the plasma membrane. Clathrin mediated endocytosis (CME) is one of the most commonly used endocytic mechanisms in mammalian cells and its mechanism has been intensively studied over the years. Clathrin with the help of other adaptor/accessory proteins are able to form vesicles in the plasma membrane which are removed from the membrane by dynamin. There are many other kinds of internalization pathways which include phagocytosis, macropinocytosis, caveolae-dependent endocytosis, and caveolae and clathrin-independent endocytosis. In the first part of the thesis, we characterized a newly identified WVQF motif containing, AP2-binding protein, NECAP1 in neurons. We found that NECAP1 plays a vital role in the CME of transferrin and synaptotagmin in neuronal cells. In the second part, we studied endocytosis of nerve growth factor (NGF) receptor (TrkA) in PC 12 cells. At a low dose (1 ng/ml) of NGF, we found that CME of TrkA is AP2- and NECAP1-independent in PC12 cells and that beta arrestin 1 can act as an alternate adaptor for its internalization. At higher extracellular concentration of NGF, uptake is clathrin- and dynamin- and beta-arrestin 1-independent, but requires actin, Cdc42 and sphingolipids, suggesting a different pathway. Our results show that large extracellular concentrations of NGF lead to strong signals of finite duration which is later terminated by degradation of NGF or NGF-TrkA whereas low concentrations of NGF leads to long lived signals. In the third chapter, we characterized newly identified Rabs, mainly Rab18 and Rab43. We found that Rab18 is involved in COPI independent trafficking of cargo beta-1,4-galactosyltransferase (Galtase)-YFP suggesting its role in retrograde trafficking from Golgi to ER, whereas Rab43 has a regulatory role in the interaction between microtubule and pre-Golgi intermediates possibly via interaction with motor proteins. Taken together, the data in this thesis contribute to our understanding of the endocytic and secretory pathways of mammalian cells."--
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.
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.
Molecular Biology Of The Cell
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Author : Bruce Alberts
language : en
Publisher:
Release Date : 2002
Molecular Biology Of The Cell written by Bruce Alberts and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2002 with Cytology categories.
Handbook Of Neurochemistry
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Author : Abel Lajtha
language : en
Publisher:
Release Date : 1982
Handbook Of Neurochemistry written by Abel Lajtha and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1982 with Neurochemistry categories.
Intercellular Communication In The Nervous System
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Author : Robert Malenka
language : en
Publisher: Academic Press
Release Date : 2010-05-22
Intercellular Communication In The Nervous System written by Robert Malenka and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010-05-22 with Science categories.
Intercellular communication is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their environment is the basis of growth and development, tissue repair, and immunity as well as normal tissue homeostasis. Errors in cellular information processing are responsible for diseases such as cancer, autoimmunity, diabetes, and neurological and psychiatric disorders. There is substantial drug development concentrating on this and intercellular communication is the basis of much of neuropharmacology. By understanding cell signaling, diseases may be treated effectively and, theoretically, artificial tissues may be yielded. Neurotransmitters/receptors, synaptic structure and organization, gap junctions, neurotrophic factors and neuropeptides are all explored in this volume, as are the ways in which signaling controls neuroendocrinology, neuroimmunology and neuropharmacology. Intercellular Communication in the Nervous System provides a valuable desk reference for all scientists who consider signaling. * Chapters offer impressive scope with topics addressing neurotransmitters/receptors, synaptic structure and organization, neuropeptides, gap junctions, neuropharmacology and more * Richly illustrated in full color with over 200 figures * Contributors represent the most outstanding scholarship in the field, with each chapter providing fully vetted and reliable expert knowledge