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Synuclein Regulates Synaptic Vesicle Clustering and Docking at a Vertebrate Synapse
Neurotransmission relies critically on the exocytotic release of neurotransmitters from small synaptic vesicles (SVs) at the active zone. Therefore, it is essential for neurons to maintain an adequate pool of SVs clustered at synapses in order to sustain efficient neurotransmission. It is well estab...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8660973/ https://www.ncbi.nlm.nih.gov/pubmed/34901020 http://dx.doi.org/10.3389/fcell.2021.774650 |
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author | Fouke, Kaitlyn E. Wegman, M. Elizabeth Weber, Sarah A. Brady, Emily B. Román-Vendrell, Cristina Morgan, Jennifer R. |
author_facet | Fouke, Kaitlyn E. Wegman, M. Elizabeth Weber, Sarah A. Brady, Emily B. Román-Vendrell, Cristina Morgan, Jennifer R. |
author_sort | Fouke, Kaitlyn E. |
collection | PubMed |
description | Neurotransmission relies critically on the exocytotic release of neurotransmitters from small synaptic vesicles (SVs) at the active zone. Therefore, it is essential for neurons to maintain an adequate pool of SVs clustered at synapses in order to sustain efficient neurotransmission. It is well established that the phosphoprotein synapsin 1 regulates SV clustering at synapses. Here, we demonstrate that synuclein, another SV-associated protein and synapsin binding partner, also modulates SV clustering at a vertebrate synapse. When acutely introduced to unstimulated lamprey reticulospinal synapses, a pan-synuclein antibody raised against the N-terminal domain of α-synuclein induced a significant loss of SVs at the synapse. Both docked SVs and the distal reserve pool of SVs were depleted, resulting in a loss of total membrane at synapses. In contrast, antibodies against two other abundant SV-associated proteins, synaptic vesicle glycoprotein 2 (SV2) and vesicle-associated membrane protein (VAMP/synaptobrevin), had no effect on the size or distribution of SV clusters. Synuclein perturbation caused a dose-dependent reduction in the number of SVs at synapses. Interestingly, the large SV clusters appeared to disperse into smaller SV clusters, as well as individual SVs. Thus, synuclein regulates clustering of SVs at resting synapses, as well as docking of SVs at the active zone. These findings reveal new roles for synuclein at the synapse and provide critical insights into diseases associated with α-synuclein dysfunction, such as Parkinson’s disease. |
format | Online Article Text |
id | pubmed-8660973 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86609732021-12-11 Synuclein Regulates Synaptic Vesicle Clustering and Docking at a Vertebrate Synapse Fouke, Kaitlyn E. Wegman, M. Elizabeth Weber, Sarah A. Brady, Emily B. Román-Vendrell, Cristina Morgan, Jennifer R. Front Cell Dev Biol Cell and Developmental Biology Neurotransmission relies critically on the exocytotic release of neurotransmitters from small synaptic vesicles (SVs) at the active zone. Therefore, it is essential for neurons to maintain an adequate pool of SVs clustered at synapses in order to sustain efficient neurotransmission. It is well established that the phosphoprotein synapsin 1 regulates SV clustering at synapses. Here, we demonstrate that synuclein, another SV-associated protein and synapsin binding partner, also modulates SV clustering at a vertebrate synapse. When acutely introduced to unstimulated lamprey reticulospinal synapses, a pan-synuclein antibody raised against the N-terminal domain of α-synuclein induced a significant loss of SVs at the synapse. Both docked SVs and the distal reserve pool of SVs were depleted, resulting in a loss of total membrane at synapses. In contrast, antibodies against two other abundant SV-associated proteins, synaptic vesicle glycoprotein 2 (SV2) and vesicle-associated membrane protein (VAMP/synaptobrevin), had no effect on the size or distribution of SV clusters. Synuclein perturbation caused a dose-dependent reduction in the number of SVs at synapses. Interestingly, the large SV clusters appeared to disperse into smaller SV clusters, as well as individual SVs. Thus, synuclein regulates clustering of SVs at resting synapses, as well as docking of SVs at the active zone. These findings reveal new roles for synuclein at the synapse and provide critical insights into diseases associated with α-synuclein dysfunction, such as Parkinson’s disease. Frontiers Media S.A. 2021-11-26 /pmc/articles/PMC8660973/ /pubmed/34901020 http://dx.doi.org/10.3389/fcell.2021.774650 Text en Copyright © 2021 Fouke, Wegman, Weber, Brady, Román-Vendrell and Morgan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Fouke, Kaitlyn E. Wegman, M. Elizabeth Weber, Sarah A. Brady, Emily B. Román-Vendrell, Cristina Morgan, Jennifer R. Synuclein Regulates Synaptic Vesicle Clustering and Docking at a Vertebrate Synapse |
title | Synuclein Regulates Synaptic Vesicle Clustering and Docking at a Vertebrate Synapse |
title_full | Synuclein Regulates Synaptic Vesicle Clustering and Docking at a Vertebrate Synapse |
title_fullStr | Synuclein Regulates Synaptic Vesicle Clustering and Docking at a Vertebrate Synapse |
title_full_unstemmed | Synuclein Regulates Synaptic Vesicle Clustering and Docking at a Vertebrate Synapse |
title_short | Synuclein Regulates Synaptic Vesicle Clustering and Docking at a Vertebrate Synapse |
title_sort | synuclein regulates synaptic vesicle clustering and docking at a vertebrate synapse |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8660973/ https://www.ncbi.nlm.nih.gov/pubmed/34901020 http://dx.doi.org/10.3389/fcell.2021.774650 |
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