Protein Trafficking in Neurons

Protein Trafficking in Neurons
Author: Andrew J. Bean
Publsiher: Elsevier
Total Pages: 464
Release: 2006-10-27
ISBN: 9780080465890
Category: Science
Language: EN, FR, DE, ES & NL

Protein Trafficking in Neurons Book Excerpt:

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

Involvement of Myosin V and Associated Proteins in Protein Trafficking and Neuronal Morphogenesis

Involvement of Myosin V and Associated Proteins in Protein Trafficking and Neuronal Morphogenesis
Author: Anonim
Publsiher: Unknown
Total Pages: 135
Release: 2009
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

Involvement of Myosin V and Associated Proteins in Protein Trafficking and Neuronal Morphogenesis Book Excerpt:

Proper neuronal development and function requires precise sorting and delivery of various elements from the soma to the synapse. Important mediators of intracellular transport events are the actin-based class V myosin motors, which are involved in organelle transport in various cell types. Two myosin V family members, myosin Va and Vb, are present in the brain, however, the identity of cargoes transported by these motors is unknown. The objective of this thesis was to conduct molecular and cell biological studies to identify and characterize novel myosin V cargoes in neurons. The first approach I used was to characterize the distribution of candidate protein cargoes after blocking the function of endogenous myosin Va and Vb with dominant-negative (DN) versions. I found that in developing neurons, expression of DN myosin Vb, but not DN myosin Va, resulted in the accumulation in the soma of the AMPA-type glutamate receptor subunit, GluR1, and a reduction of its surface expression. I also found that myosin Vb-mediated trafficking of GluR1 required an interaction with the GTPase Rab11. These results reveal a novel mechanism for the transport of a specific glutamate receptor subunit mediated by myosin Vb and Rab11. As an alternative approach to identify myosin Va binding partners in the brain, we conducted a yeast-two hybrid screen of a rat brain cDNA library using the cargo binding domain of myosin Va. Among the proteins identified in our screen, I selected a protein of unknown function previously identified as Rab-lysosomal-interacting protein like 2 (RILPL2) and further assessed its function. I found that RILPL2 expression in non-neuronal cells resulted in morphological changes and activation of the Rho GTPase Rac1. In developing neurons, gain or loss of RILPL2 function altered the density of dendritic spine protrusions and increased phosphorylation of the Rac1 effector Pak. These findings uncover a novel role for the myosin Va-interacting protein, RILPL2, in regulati.

The Neuronal Cytoskeleton Motor Proteins and Organelle Trafficking in the Axon

The Neuronal Cytoskeleton  Motor Proteins  and Organelle Trafficking in the Axon
Author: Anonim
Publsiher: Academic Press
Total Pages: 534
Release: 2016-01-12
ISBN: 0128033541
Category: Science
Language: EN, FR, DE, ES & NL

The Neuronal Cytoskeleton Motor Proteins and Organelle Trafficking in the Axon Book Excerpt:

The Neuronal Cytoskeleton, Motor Proteins, and Organelle Trafficking in the Axon, a new volume in the Methods in Cell Biology series continues the legacy of this premier serial with quality chapters authored by leaders in the field. This volume covers research methods in neuronal cells, and includes sections on such topics as actin transport in axons and neurofilament transport. Covers an increasingly appreciated field in cell biology Includes both established and new technologies Contributed by experts in the field

Local Biosynthetic Trafficking of Synaptic Proteins in Neuronal Dendrites

Local Biosynthetic Trafficking of Synaptic Proteins in Neuronal Dendrites
Author: Aaron Benjamin Bowen
Publsiher: Unknown
Total Pages: 193
Release: 2017
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

Local Biosynthetic Trafficking of Synaptic Proteins in Neuronal Dendrites Book Excerpt:

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.

Protein Kinesis

Protein Kinesis
Author: Anonim
Publsiher: CSHL Press
Total Pages: 843
Release: 1995
ISBN: 9780879690694
Category: Science
Language: EN, FR, DE, ES & NL

Protein Kinesis Book Excerpt:

Investigators provide an account of how cells control and repair the folding of newly synthesized proteins and transport them correctly to membranes, mitochondria and other cellular addresses. It also provides information on synaptic function, cell movement and other cellular functions.

Membrane Trafficking and Endocytosis in Neurons

Membrane Trafficking and Endocytosis in Neurons
Author: Ayesha Murshid
Publsiher: Unknown
Total Pages: 135
Release: 2008
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

Membrane Trafficking and Endocytosis in Neurons Book Excerpt:

"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."--

Intracellular Traffic and Neurodegenerative Disorders

Intracellular Traffic and Neurodegenerative Disorders
Author: Peter H. St.George-Hyslop,William C. Mobley
Publsiher: Springer Science & Business Media
Total Pages: 184
Release: 2009-02-03
ISBN: 3540879412
Category: Medical
Language: EN, FR, DE, ES & NL

Intracellular Traffic and Neurodegenerative Disorders Book Excerpt:

Many adult onset neurodegenerative diseases arise from the accumulation of misfolded peptides. This book examines the role sub-cellular trafficking pathways play in the pathological accumulation of these misfolded proteins and in attempts to clear them.

Trafficking of Prion Protein in Adult Sensory Neurons

Trafficking of Prion Protein in Adult Sensory Neurons
Author: Celia J. Parkyn,King's College London. Guy's, King's and St. Thomas's School of Medicine
Publsiher: Unknown
Total Pages: 540
Release: 2007
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

Trafficking of Prion Protein in Adult Sensory Neurons Book Excerpt:

The Neuronal Functions of EF hand Ca 2 binding Proteins 2nd Edition

The Neuronal Functions of EF hand Ca 2   binding Proteins 2nd Edition
Author: Michael R. Kreutz,José R. Naranjo,Karl-Wilhelm Koch,Beat Schwaller
Publsiher: Frontiers Media SA
Total Pages: 212
Release: 2016-11-01
ISBN: 2889450031
Category: Electronic Book
Language: EN, FR, DE, ES & NL

The Neuronal Functions of EF hand Ca 2 binding Proteins 2nd Edition Book Excerpt:

Ca2+ signaling in neurons is characterized by highly restricted and dynamic gradients called Ca2+ waves, spikes, transients and puffs depending upon their corresponding spatial and temporal features. Based on this strict segmentation the Ca2+ ion provides a versatile basis for complex signaling in neuronal subcompartments with a spatial resolution of micro- and nanodomains. The multitude of Ca2+-regulated processes requires specialized downstream processing machinery, translating the Ca2+ signal into alterations of cellular processes. The broad range of different Ca2+-triggered phenomena in neurons, ranging from neurotransmission to gene expression, is reflected by the existence of a multitude of different Ca2+-binding proteins (CaBPs) from which numerous belong to the EF-hand super-family. EF-hand proteins can be subdivided into Ca2+ buffer and Ca2+ sensor proteins. Whereas the first group has a very high affinity for Ca2+, exhibits little conformational change in the Ca2+-bound state and is thought to mainly chelate Ca2+, the second group has a lower affinity for Ca2+ and shows considerable conformational changes upon Ca2+-binding, which usually triggers a target interaction. Neuronal calcium sensor (NCS) proteins and the related Caldendrin/CaBP/Calneuron (nCaBPs) proteins are members of this latter group. They resemble the structure of their common ancestor Calmodulin (CaM) with four EF-hand Ca2+-binding motifs, of which not all are functional. However, despite their structural homology with CaM, NCS as well as nCaBPs are quite diverse in amino acid sequence. It is therefore surprising that relatively few binding partners have been identified that are not CaM targets and this raises the question of the specificity and function of these interactions. In terms of function, binding of NCS and nCaBP has frequently different consequences than binding of CaM, which substantially increases the versatility of the Ca2+ tool kit. The general idea of this special issue is to provide an overview on the function of neuronal EF-hand calcium-binding proteins in health and disease. But we will not just provide a mere collection of articles to stress the function of each protein. The issue will mainly deal with emerging concepts on Ca2+-signaling/buffering mediated by EF-hand Ca2+-binding proteins. This includes questions like features that define the functional role of a EF-hand calcium sensor in neurons, the conditions that make physiological relevance of a given interaction of a CaBP with its target plausible, the emerging synaptic role of these proteins, and mounting evidence for their role in the regulation of protein trafficking. Structural aspects and biophysical studies will be covered. Another aspect will be the role of CaBPs in brain disease states. This aspect includes studies showing that CaBPs are targets of drugs in clinical use, studies showing that expression levels of calcium-binding proteins are frequently altered in brain disease states as well as reports on mutations in EF-hand calcium sensors linked to human disease.

Synaptojanin1 is Involved in Endolysosomal Trafficking in Cone Photoreceptors

Synaptojanin1 is Involved in Endolysosomal Trafficking in Cone Photoreceptors
Author: Ashley Amelia George
Publsiher: Unknown
Total Pages: 86
Release: 2015
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

Synaptojanin1 is Involved in Endolysosomal Trafficking in Cone Photoreceptors Book Excerpt:

Cells require the ability to properly sort and traffic proteins to their correct subcellular destination. The production of new proteins must be balanced by the turnover of old and damaged proteins. A breakdown in this process is detrimental to any cell; however highly polarized, non-proliferating cells, such as neurons, are particularly vulnerable to defects in protein turnover. Photoreceptors are highly polarized, specialized neurons that have high protein trafficking demands. At one end of the photoreceptor is the outer segment; the site of photon detection and phototransduction. The outer segment requires a constant supply of new proteins and membranes to maintain proper function. At the opposite end of the cell is the site of synaptic transmission. The synapse also undergoes large amounts of membrane trafficking and turnover due to the release of neurotransmitter and subsequent synaptic vesicle recycling. Although both ends of the photoreceptor require efficient membrane trafficking, the majority of studies of protein trafficking in photoreceptors have focused on the outer segment. In addition, photoreceptors do not need to degrade old and damaged proteins and membranes from the outer segment; the retinal pigment epithelium phagocytoses outer segment discs. Therefore the focus on outer segment trafficking has resulted in a deficit in our understanding of the process of protein degradation in photoreceptor cells. In this study we establish that the zebrafish nrca14 mutant has a specific defect in endolysosomal and autophagic trafficking and can therefore be used as a model to understand these processes in cone photoreceptors. The trafficking defects in the nrca14 cones begin early in photoreceptor development. The accumulation of autophagosomes in the nrca14 mutant is due, at least in part, to impaired autophagosome maturation that is not caused by a decrease in autophagosome mobility. The causative mutation in the nrca14mutant is in the gene encoding a polyphosphoinositide phosphatase Synaptojanin1; highlighting the importance of the phosphoinositide lipids in protein degradation pathways. We analyzed the distribution of the phosphoinositides PI(3)P, PI(4)P, PI(3,5)P2 and PI(4,5)P2 in wild type and nrca14 photoreceptors. We found that the distribution of these lipids in wild type photoreceptors is the same as in non-neuronal cell types; PI(3)P on endosomes, PI(4)P on the Golgi, PI(3,5)P2 on late endosomes/lysosomes and PI(4,5)P2 in the plasma membrane. We found no gross change in the distribution of these phosphoinositides in nrca14 mutant photoreceptors. Further, we use the nrca14 mutant phenotypes to discover that the Synaptojanin1 dephosphorylates a PIP species with a 5'phosphate to regulate autophagy and endolysosomal trafficking. Collectively, my work has generated a large tool set for studying membrane trafficking in zebrafish cone photoreceptors and has defined a specific role for Synaptojanin1 in regulating autophagy and degradative trafficking pathways in cones.

Author: Anonim
Publsiher: Unknown
Total Pages: 135
Release: 1978
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

Book Excerpt:

Structural and Functional Organization of the Synapse

Structural and Functional Organization of the Synapse
Author: Johannes W. Hell,Michael D. Ehlers
Publsiher: Springer Science & Business Media
Total Pages: 801
Release: 2008-06-25
ISBN: 0387772324
Category: Medical
Language: EN, FR, DE, ES & NL

Structural and Functional Organization of the Synapse Book Excerpt:

This new Springer volume, which comes complete with a free DVD, is a comprehensive and detailed overview of the synapse with emphasis on the glutamatergic synapse. Most chapters relate the synapse’s functional aspects to its molecular mechanisms. This approach shows which mechanisms are characterized on both the functional and structural level and can thus be considered firmly established. It’s an important text for neuroscientists and disease-oriented clinicians in neurology.

Targeting Membrane Proteins to Inner Segments of Vertebrate Photoreceptors

Targeting Membrane Proteins to Inner Segments of Vertebrate Photoreceptors
Author: Yuan Pan
Publsiher: Unknown
Total Pages: 142
Release: 2015
ISBN: 1928374650XXX
Category: Membrane proteins
Language: EN, FR, DE, ES & NL

Targeting Membrane Proteins to Inner Segments of Vertebrate Photoreceptors Book Excerpt:

Autophagy of the Nervous System

Autophagy of the Nervous System
Author: Zhenyu Yue,Charleen T Chu
Publsiher: World Scientific
Total Pages: 440
Release: 2012-10-01
ISBN: 981444068X
Category: Science
Language: EN, FR, DE, ES & NL

Autophagy of the Nervous System Book Excerpt:

What is autophagy? Why would neurons digest parts of themselves through autophagy? How can autophagy save the lives of cells under some conditions, but act as an accomplice to cell death in others? By what mechanisms are autophagy-related processes dysregulated in neurological diseases, and are there therapeutic strategies to correct or compensate for their dysfunction? This book provides an expert view of major concepts in autophagy research with a focus on autophagy in neurons. Experimental evidence for evolutionarily conserved and specialized regulatory mechanisms for autophagy in the mammalian nervous system will be presented, including recent data on braking mechanisms. Areas of intersection with cell death, the ubiquitin-proteasome system, chaperone-mediated autophagy, and the endocytic pathway will be reviewed, along with emerging areas of mitochondrial autophagy (mitophagy) and the autophagic regulation of neuritic/synaptic processes. Advances in delineating mechanisms by which autophagy is involved in the pathophysiology of neurological disorders, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, ischemia/hypoxia and lysosomal storage diseases, will be discussed along with current drug development strategies targeting autophagy. Contents:Neuronal Autophagy: Cellular Process and Regulation:The Cellular Process of Autophagy and Control of Autophagy in Neurons (Nicole C McKnight, Noboru Mizushima and Zhenyu Yue)Autophagosome Maturation, Endocytosis and Neurodegenerative Disease (Ai Yamamoto and Anne Simonsen)Cross-Talk Between the Ubiquitin-Proteasome System and Macroautophagy (Serhiy Pankiv and Terje Johansen)Chaperone-Mediated Autophagy (CMA) in Neurons (Maria Xilouri, Hsiao-Yu Peng and Leonidas Stefanis)Maintaining Autophagic Balance: A Role for Brakes (Salvatore J Cherra, III and Charleen T Chu)Autophagy and Neurological Diseases:Autophagy and Its Cross-Talk with Cell Death in Neural Development (Sabrina Di Bartolomeo and Francesco Cecconi)Autophagy in the Retina: Development, Physiology and Pathology (Patricia Boya)Genetic Mouse Models for Elucidation of Autophagy-Lysosomal Systems in Neurons Under Physiologic and Pathologic Conditions (Masaaki Komatsu, Masato Koike, Yoshinobu Ichimura and Yasuo Uchiyama)Autophagy in Amyotrophic Lateral Sclerosis (Jozsef Gal and Haining Zhu)Autophagy Failure in Alzheimer's Disease and Lysosomal Storage Disorders: A Common Pathway to Neurodegeneration? (Devin M Wolfe and Ralph Nixon)Autophagy in Huntington's and Parkinson's Diseases: Pathogenic Mechanism and Therapeutic Potentials (Junghyun Lim, Lauren G Friedman, Nicole C McKnight and Zhenyu Yue)Metabolism, Autophagy and Neurodegeneration (W Haung Yu and Karen E Duff)The Potential of Autophagy Regulation in the Treatment of Neurodegenerative Diseases (Ashley R Winslow, Zeyn W Green-Thompson and David C Rubinsztein)Lysosome Storage Disorders on the Brain: The Autophagy-Lysosome Pathway Contributes to Disease Pathophysiology and May be Utilized for Therapeutic Benefit (John J Shacka)Specialized Autophagy: The New Frontier:Autophagy — Roles in Synaptic Structure and Function (Daniela Hernandez and David Sulzer)Neuronal Mitochondrial Transport and Turnover via Mitophagy (Zu-Hang Sheng and Charleen T Chu)Role of Autophagy in Neurite Degeneration In Vitro (Yi Yang, Xiaoxiang Zheng and Tatsuro Koike) Readership: Neurologists (clinical), molecular biologists (scientists), and college students. Keywords:Autophagy;Neurons;Neurodegeneration;Cell Death;Disease;Neuropathology;Neurological Disorders;Autophagosomes;Lysosomes;Degradation;Axons;Mitochondria;Chaperone Proteins;Alzheimer's Disease;Parkinson's Disease;Huntington's Disease;Protein AggregationKey Features:Collates the most recent research on autophagy regulation and critically examines the relevance of specific mechanisms to disease in light of unique aspects of neuronal cell biologyCovers newer knowledge of general autophagy processes, reviews the state of the art on specific aspects of autophagy regulation in neurons, and discusses the role of autophagy in neurodegenerative diseaseThe co-editors and contributing authors for each of the chapters are all experts, including some of the most influential figures in autophagy research and neurodegeneration

A Molecular Analysis of Protein Trafficking in the Vertebrate Retina

A Molecular Analysis of Protein Trafficking in the Vertebrate Retina
Author: Bryan L. Krock
Publsiher: Unknown
Total Pages: 135
Release: 2010
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

A Molecular Analysis of Protein Trafficking in the Vertebrate Retina Book Excerpt:

Vertebrate photoreceptors are highly specialized sensory neurons that utilize a modified cilium known as the outer segment to detect light. Proper trafficking of proteins to the outer segment is essential for photoreceptor function and survival and defects in this process lead to retinal disease. In this dissertation I focus on two aspects of protein trafficking, intracellular vesicular trafficking in photoreceptors and retinal pigmented epithelial (RPE) cells and how it relates to the human disease choroideremia (CHM), and the trafficking of proteins through the photoreceptor cilium. The human retinal degenerative disease choroideremia (CHM) is caused by mutation of the Rab escort protein-1 (REP1) gene, which is required for proper intracellular vesicular trafficking. However, it was unclear whether photoreceptor degeneration in this disease is cell-autonomous, due to defective opsin transport within the photoreceptor, or is noncell-autonomous and a secondary consequence of defective RPE. Utilizing the technique of blastomere transplantation and a zebrafish line with a mutation in the rep1 gene, I show that photoreceptor degeneration in CHM is noncell-autonomous and is caused by defective RPE. The molecular machinery responsible for protein trafficking through the photoreceptor cilium remained unclear for a long time. Recent studies found Intraflagellar Transport (IFT) is the process that mediates cilia formation and transport of proteins through a cilium, and further analyses showed IFT is important for trafficking proteins to the outer segment. However, many details about how IFT works in photoreceptors remained unclear. By analyzing zebrafish harboring a null mutation in the ift57 gene, I show that Ift57 is only required for efficient IFT, and that the Ift57 protein plays a role in the ATP-dependent dissociation of kinesin II from the IFT particle. Lastly, I investigate the role of retrograde IFT in photoreceptors, a process that had yet to be investigated. By utilizing antisense morpholino oligonucleotides to inhibit expression of cytoplasmic dynein-2 (the molecular motor that mediates retrograde IFT), I show that retrograde IFT is required for outer segment extension and the recycling of IFT proteins.

Molecular Biology of the Neuron

Molecular Biology of the Neuron
Author: F. R. Davies,Brian Morris,Ibls Division of Neuroscience and Biomedical Systems Brian J Morris
Publsiher: Oxford University Press
Total Pages: 480
Release: 2004-04-08
ISBN: 9780198509981
Category: Medical
Language: EN, FR, DE, ES & NL

Molecular Biology of the Neuron Book Excerpt:

This book is a valuable compendium of up-to-date reviews of neuronal molecular biology by leading researchers in the field. It covers all aspects of neuron structure and function, with the emphasis on genetic and molecular analysis.

Cell Biology of the Axon

Cell Biology of the Axon
Author: Edward Koenig
Publsiher: Springer Science & Business Media
Total Pages: 360
Release: 2009-09-01
ISBN: 9783642030192
Category: Science
Language: EN, FR, DE, ES & NL

Cell Biology of the Axon Book Excerpt:

Recent years have witnessed striking advances in research on axons at a cellular level that substantially impact our current understanding of axonal biology. Newer findings and their ramifications are critically reviewed in the 16 chapters of this volume by authors highly qualified by virtue of their scientific contributions to research areas they know and write about. Five basic areas (I to V) germane to axonal biology are highlighted, beginning with (I) signaling interactions mediating myelination, and differentiation of axonal membrane domains; (IIa) issues surrounding organization and transport dynamics of neurofilaments in axons, (IIb) mechanisms regulating microtubule organization and dynamics, misregulation of which causes axonal degeneration, and (IIc) the roles actin binding proteins play in regulating organization and functions of the actin filament system in mature and growing axons; (IIIa) myosin motor proteins and cargoes intrinsic to the axon compartment, (IIIb) mitochondrial transport motors, and imperatives governing transport dynamics and directional delivery, (IIIc) mechanisms mediating retrograde signaling associated with NGF’s role in trophic-dependent neuronal survival, and (IIId) potential for impaired subcellular targeting of a -synuclein as a mechanism for accumulation of Lewy body inclusions in synucleinopathies; (IVa) occurrence and organization of discrete ribosome-containing domains in axons, (IVb) endogenous mRNAs, classes of proteins translated locally, and RNP trafficking in axons, (IVc) importance of locally synthesized nuclear encoded mitochondrial proteins for maintenance, function and survival of axons, (IVd) occurrence of RNA trafficking from glial cells to axons, and significance glial RNA transcripts may play in expression in axons and axon terminals, (IVe) RNA trafficking and localization of RNA transcripts in axonal growth cones, and signaling pathways that modulate local protein synthesis for directional elongation, and (IVf) genetic and molecular defects underlying spinal muscular atrophy, and roles that SMN gene product plays as a molecular chaperone in mRNA transport and translation; (Va) injury-induced local synthesis of a protein forming a retrograde signaling complex in axons to stimulate regeneration, and (Vb) endogenous and exogenous factors that condition axonal regenerative capacity in PNS and CNS, including injury-induced activation of specific genes governing regeneration. Emergent complexities revealed in this volume compel a major revision in the traditional conceptual model of the axon’s intrinsic makeup and capacities.

Trafficking of Scaffolding and Adhesion Proteins

Trafficking of Scaffolding and Adhesion Proteins
Author: Anonim
Publsiher: Unknown
Total Pages: 135
Release: 2008
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

Trafficking of Scaffolding and Adhesion Proteins Book Excerpt:

Part One: Role of a pre-formed scaffolding complex in excitatory synapse formation. In order to determine the role of non-synaptic clusters of postsynaptic proteins we monitored the trafficking of several candidate proteins implicated in synaptogenesis, when non-synaptic clusters of scaffold proteins are most abundant. We found a protein complex consisting of two populations that differ in their content, mobility, and involvement in synapse formation. One subpopulation is mobile and relies on actin transport for delivery to nascent and existing synapses. These mobile clusters contain the scaffolding proteins PSD-95, GKAP, and Shank. The second group consists of stationary non-synaptic scaffold complexes that mainly contain neuroligin-1, can recruit synaptophysin-containing axonal transport vesicles, and are readily transformed to functional presynaptic contacts that recycle the vital dye FM 4-64. These results postulate a mechanism whereby preformed scaffold protein complexes serve as predetermined postsynaptic hotspots for establishment of new functional excitatory synapses. Part Two: Neuroligin trafficking in live neurons. The mechanisms that govern the differential trafficking and retention of neuroligin-1 to glutamatergic synapses and neuroligin-2 to GABAergic synapses remain unclear. In order to monitor the recruitment/retention of neuroligin-1 and -2 to synaptic sites, a site-specific biotinylation-based approach was utilized that allows for the visualization of surface proteins in live neurons with monovalent streptavidin. To quantify these changes, FRAP (fluorescence recovery after photo beaching) showed similar recovery rates for GFP-tagged neuroligins (representative of the total pool) compared to AP-tagged neuroligins (representative of the surface pool). The mobile pool of neuroligin-1 clusters was significantly larger than neuroligin-2 clusters and was depressed in older neurons. The mobility of neuroligin-1 clusters was influenced by the expression of.

Structure Function and Modulation of Neuronal Voltage Gated Ion Channels

Structure  Function  and Modulation of Neuronal Voltage Gated Ion Channels
Author: Valentin K. Gribkoff,Leonard K. Kaczmarek
Publsiher: John Wiley & Sons
Total Pages: 496
Release: 2008-12-09
ISBN: 0470429895
Category: Science
Language: EN, FR, DE, ES & NL

Structure Function and Modulation of Neuronal Voltage Gated Ion Channels Book Excerpt:

This book discusses voltage-gated ion channels and their importance in drug discovery and development. The book includes reviews of the channel genome, the physiological bases of targeting ion channels in disease, the unique technologies developed for ion channel drug discovery, and the increasingly important role of ion channel screening in cardiac risk assessment. It provides an important reference for research scientists and drug discovery companies.

Regulation of Dynein dependent Neuronal Transport and Trafficking by CDK5

Regulation of Dynein dependent Neuronal Transport and Trafficking by CDK5
Author: Eva Klinman
Publsiher: Unknown
Total Pages: 306
Release: 2016
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

Regulation of Dynein dependent Neuronal Transport and Trafficking by CDK5 Book Excerpt:

Neurons have a distinct structure; they are the only cells in the body whose proximal and distal ends can be separated by more than a meter. This leads to unique challenges for the neuron, specifically, how proteins, organelles, and other cargo synthesized in the cell body are specifically trafficked from the soma to the distal end of the axon, and how degradative cargo and signaling factors are transported from the terminal to the cell body. Using primary cultured central and peripheral neurons isolated from the brains and spinal cords of rats or mice, we sought to determine if a neuronal-specific kinase, cyclin dependent kinase 5 (CDK5) regulates the motility of cargo moving along the axon, and if this kinase also regulates the localized exclusion of somatodendritic cargo from the axon. Within the mid-axon, we observed that baseline CDK5 activity was not required to regulate axonal transport, but pathological activation of CDK5 via a stress-associated activator disrupted both anterograde (outward) and retrograde (inward) motility. In contrast, within the axon initial segment (AIS), inhibition of normal CDK5 activity disrupted cytoskeletal structure and compromised axonal and dendritic sorting, aberrantly permitting the entry of somatodendritic cargos into the axon. We determined that both roles of CDK5 in axonal regulation were dependent on phosphorylation of target Ndel1, a protein that regulates the interaction of the retrograde microtubule-based motor dynein with its cofactor Lis1. In the mid-axon, high levels of CDK5 activity causes dynein to tightly bind along the microtubule interrupting processive motility, while in the AIS, CDK5 activity is required to initiate dynein-driven return of somatodendritic cargo to the cell body. Together theses studies demonstrate the importance of CDK5 activity in the regulation of transport within the neuron.