Regulation Of Synaptic Structure And Function At The Drosophila Neuromuscular Junction
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Regulation Of Synaptic Structure And Function At The Drosophila Neuromuscular Junction
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Author : Aline Dorret Blunk
language : en
Publisher:
Release Date : 2013
Regulation Of Synaptic Structure And Function At The Drosophila Neuromuscular Junction written by Aline Dorret Blunk and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013 with categories.
Neuronal communication requires a spatially organized synaptic apparatus to coordinate neurotransmitter release from synaptic vesicles and activation of postsynaptic receptors. Structural remodeling of synaptic connections can strengthen neuronal communication and synaptic efficacy during development and behavioral plasticity. Here, I describe experimental approaches that have revealed how the actin cytoskeleton participates in transynaptic signaling to control synapse assembly. I also describe my studies on how regulation of endocytic trafficking controls synaptic growth during neuronal development. To identify regulators of synapse assembly, I carried out a large-scale EMS mutagenesis screen of the second chromosome. From this screen I identified a mutation in actin 57B that disrupts synaptic morphology and presynaptic active zone organization. Actin 57B is one of six actin genes in Drosophila and is expressed in body wall muscle during larval development. The isolated allele harbors a point mutation disrupting a highly conserved amino acid present throughout the actin family. Homozygous mutant larvae show impaired alignment and spacing of presynaptic active zones. Additionally, disruption of the organization of the postsynaptic density is observed, with mislocalization of the Spectrin cytoskeleton and the PSD-homolog Disc-Large. Phallodin staining reveals a severe disruption of postsynaptic actin surrounding presynaptic boutons, with the formation of aberrant large actin swirls. Based on these results, we hypothesize that the loss of a synaptic interaction mediated by actin 57B leads to disruption of postsynaptic cytoskeletal organization and dysregulation of signals required to organize presynaptic active zones. Additionally, I present data that provide new insights into the mechanisms controlling synaptic growth signaling during transit through the endocytic pathway. Nervous Wreck (Nwk) is a presynaptic F-BAR/SH3 protein that regulates synaptic growth signaling in Drosophila. Here, I show that Nwk acts through a physical interaction with Sorting Nexin 16 (SNX16). SNX16 promotes synaptic growth signaling by activated BMP receptors, and live imaging in neurons reveals that SNX16-positive early endosomes undergo transient interactions with Nwkcontaining recycling endosomes. We identify an alternative signal termination pathway in the absence of Snx16 that is controlled by ESCRT-mediated internalization of receptors into the endosomal lumen. Our results define a presynaptic trafficking pathway mediated by SNX116, NWK and the ESCRT complex that functions to control synaptic growth signaling at the interface between endosomal compartments. Together, these experiments have expanded our understanding of the molecular mechanisms that control synaptic growth and assembly, highlighting the role of the postsynaptic actin cytoskeleton and the presynaptic endosomal trafficking pathway as key regulators.
Regulation Of Synaptic Structure And Function
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Author : Zhiyong Shao
language : en
Publisher: Frontiers Media SA
Release Date : 2022-11-18
Regulation Of Synaptic Structure And Function written by Zhiyong Shao 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 2022-11-18 with Science categories.
Synaptic Structure And Function At The Drosophila Larval Neuromuscular Junction
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Author : Lauren Kaye Buhl
language : en
Publisher:
Release Date : 2011
Synaptic Structure And Function At The Drosophila Larval Neuromuscular Junction written by Lauren Kaye Buhl and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with categories.
From yeast to humans, the fusion of vesicles with target membranes is driven by the formation of a parallel four-helix bundle of SNARE proteins that are present on both the vesicular (v-SNAREs) and target plasma membranes (t-SNAREs). The full zippering of this bundle is thought to provide the driving force for membrane fusion. At synapses, vesicle fusion is exquisitely regulated by Ca2+ such that neurotransmitter release can occur within 1 ms of an action potential reaching the presynaptic terminal. This feat implies the presence of both a Ca2+ sensor and a fusion clamp that prevents vesicles from fusing in the absence of Ca2+. The presynaptic Ca2+ sensor for synchronous vesicle release is widely accepted to be Synaptotagmin-1 (Syt1), and there is growing evidence that Complexin (Cpx), which binds to the SNARE complex with high affinity and 1:1 stoichiometry, can act as a vesicle fusion clamp. As suggested by its name, however, Cpx appears to play a more complex role in vesicle release, carrying out different functions in spontaneous vs. evoked fusion events. Here we show the Drosophila express at least two Cpx isoforms that differ in the C-terminus (Cpx7A and Cpx7B) and can be further regulated by RNA editing and phosphorylation. These isoforms show different effects on spontaneous vs. evoked neurotransmitter release, with Cpx7A being a better fusion clamp and Cpx7B being a better fusion promoter. In addition, these isoforms have different effects on synaptic growth, which may be linked to their effects on synaptic physiology.
Regulation Of Synaptic Plasticity At The Drosophila Larval Nmj
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Author : Maude Warren-Paquin
language : en
Publisher:
Release Date : 2008
Regulation Of Synaptic Plasticity At The Drosophila Larval Nmj written by Maude Warren-Paquin 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.
Neuromuscular Junctions In Drosophila
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Author :
language : en
Publisher: Academic Press
Release Date : 1999-04-29
Neuromuscular Junctions In Drosophila written by and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 1999-04-29 with Science categories.
Neuromuscular Junctions in Drosophila gathers the main contributions that research using the fruit fly Drosophila melanogaster has made in the area of synapse development, synapse physiology, and excitability of muscles and nerve cells. The chapters in this book represent a synthesis of major advances in our understanding of neuronal development and synaptic physiology, which have been obtained using the above approach.This book is directed to the general neuroscience audience: researchers, instructors, graduate students, and advanced undergraduates who are interested in the mechanisms of synapse development and physiology. However, the book will also be a valuable resource for those that use the fruit fly as a model system in their laboratories. Key Features* Synthesizes the genetic approaches used to study synaptic development and function at the neuromuscular junction, using flies as a model system* Covers major recent advances in muscle development, pathfinding, synapse maturation and plasticity, exo- and endocytosis, and ion channel function* Written in clear language that is easily understandable to readers not already familiar with fruit fly research* Includes numerous diagrams and extensive reference lists
Mechanisms Controlling The Formation And Growth Of Synapses At The Neuromuscular Junction Of Drosophila Melanogaster
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Author : Karen Marie Zito
language : en
Publisher:
Release Date : 1998
Mechanisms Controlling The Formation And Growth Of Synapses At The Neuromuscular Junction Of Drosophila Melanogaster written by Karen Marie Zito and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1998 with categories.
Analysis Of Neuropeptide Signaling In The Regulation Of Synaptic Growth In Drosophila
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Author :
language : en
Publisher:
Release Date : 2012
Analysis Of Neuropeptide Signaling In The Regulation Of Synaptic Growth In Drosophila written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012 with categories.
Synapses are the basic units of neural structure and function. Proper synaptic growth is essential for normal development of the nervous system and its function in mediating complex behaviors such as learning and memory. In my dissertation work, I took a combined approach of genetics, molecular biology and biochemistry to identify genes and molecular pathways that regulate synaptic growth in Drosophila, and discovered neuropeptide signaling as a novel mechanism in this process. Neuropeptides have been known to affect neuronal excitability and the strength of synaptic transmission. However, neuropeptides have not been clearly implicated in synaptic growth and development. Through forward genetics, I discovered a cholecystokinin-like receptor (CCKLR) and its predicted ligand drosulfakinin (DSK), as components of a signaling pathway that strongly promote growth of the Drosophila larval neuromuscular junction (NMJ). Loss-of-function mutations of CCKLR or dsk produce severe NMJ undergrowth, whereas over-expression of CCKLR leads to NMJ overgrowth. Through targeted RNAi expression and transgenic rescue experiments I show that presynaptic expression of CCKLR in motor neurons is necessary and sufficient for regulation of NMJ growth. Through analysis of double mutants, I have dissected the signaling pathway downstream of the receptor. I show that this pathway involves G-protein-dependent stimulation of adenyl cyclase to activate PKA, which in turn activates CREB, the cAMP-response element binding protein. In addition, I demonstrate that DSK activates CCKLR biochemically, and that DSK/CCKLR signaling affects synaptic transmission and larval locomotor behavior. To discover novel genes that interact with the CCKLR-signaling pathway to regulate NMJ growth, I performed a modifier screen using chromosomal deficiencies. This pilot screen has identified several regions on the second and third chromosomes that dominantly enhance or suppress the NMJ phenotype of CCKLR mutants. Intriguingly, a number of neuropeptide signaling molecules were found among the candidate interacting genes. Specifically, I have found that leucokinin (DLK) and leucokinin receptor (LKR) negatively regulate NMJ growth, and strongly interact with CCKLR. The results of the modifier screen suggest that neuropeptide signaling may be a more common mechanism for regulating NMJ growth than previously realized and many of the molecules are yet to be uncovered.
The Drosophila Serrate Is Required For Synaptic Structure And Function At Larval Neuromuscular Junctions
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Author :
language : en
Publisher:
Release Date : 2010
The Drosophila Serrate Is Required For Synaptic Structure And Function At Larval Neuromuscular Junctions written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with categories.
Drosophila melanogaster is an excellent model system to identify genes involved in synaptic growth and function. In Drosophila, the Serrate (Ser) gene encodes a transmembrane protein that is a ligand for Notch receptor. Several previous studies implicated a role for Serrate in normal wing development and patterning. In this study, I demonstrate that Serrate is required for normal synaptic growth and function. I characterized the phenotype of a Serrate mutation (serB936) that was identified by an EMS-induced genetic screen aimed at identifying novel genes that play a role in synaptic growth and function. Co-localization studies show that Serrate protein is expressed at both the pre- and postsynaptic side of larval neuromuscular junctions (NMJs). Mutations in ser impair synaptic transmission at larval NMJs. This defect is entirely presynaptic, as nerve-evoked excitatory junction potentials (EJP) and quantal content (QC) of neurotransmitter release are significantly reduced when compared to wild-type control. Further, mutations in ser also alter the growth of the NMJ and the underlying muscle. Mutations in ser significantly reduce the size of larval body wall muscles (length and surface area) as well as the number and size of synaptic boutons, and the number of secondary axonal branches. Ubiquitous or muscle-specific expression of normal Serrate in serB936 mutants restores a normal muscle size but not a normal size and structure of the innervating NMJ. However, expression of normal Serrate in the motor axon restores a normal number of synaptic boutons and secondary branches at serB936 mutant NMJs. In addition, it restores normal neurotransmitter release. These data suggest that Serrate protein is required presynaptically for normal synaptic growth and function. Interestingly, overexpression of Serrate in a wild type background resulted in similar phenotypes than to those of loss-of-function mutants. In conclusion, these data suggest a new functional role for Serrate in synaptic growth and function.
Synaptic Requirements For Glycan Modification
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Author : William Matthew Parkinson
language : en
Publisher:
Release Date : 2016
Synaptic Requirements For Glycan Modification written by William Matthew Parkinson and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016 with Electronic dissertations categories.
A Molecular And Genetic Analysis Of Neuromuscular Connectivity And Synaptic Growth In Drosophila Melanogaster
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Author : Hong Iris Wan
language : en
Publisher:
Release Date : 2000
A Molecular And Genetic Analysis Of Neuromuscular Connectivity And Synaptic Growth In Drosophila Melanogaster written by Hong Iris Wan and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2000 with categories.