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...

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Autores principales:	Kaitlyn E. Fouke, M. Elizabeth Wegman, Sarah A. Weber, Emily B. Brady, Cristina Román-Vendrell, Jennifer R. Morgan
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	exocytosis endocytosis synapsin lamprey liquid phase separation VAMP2 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0886625b70a34663bc79bc0ace005b54
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spelling	oai:doaj.org-article:0886625b70a34663bc79bc0ace005b542021-12-01T05:28:22ZSynuclein Regulates Synaptic Vesicle Clustering and Docking at a Vertebrate Synapse2296-634X10.3389/fcell.2021.774650https://doaj.org/article/0886625b70a34663bc79bc0ace005b542021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.774650/fullhttps://doaj.org/toc/2296-634XNeurotransmission 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.Kaitlyn E. FoukeKaitlyn E. FoukeM. Elizabeth WegmanSarah A. WeberSarah A. WeberEmily B. BradyCristina Román-VendrellJennifer R. MorganFrontiers Media S.A.articleexocytosisendocytosissynapsinlampreyliquid phase separationVAMP2Biology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	exocytosis endocytosis synapsin lamprey liquid phase separation VAMP2 Biology (General) QH301-705.5
spellingShingle	exocytosis endocytosis synapsin lamprey liquid phase separation VAMP2 Biology (General) QH301-705.5 Kaitlyn E. Fouke Kaitlyn E. Fouke M. Elizabeth Wegman Sarah A. Weber Sarah A. Weber Emily B. Brady Cristina Román-Vendrell Jennifer R. Morgan Synuclein Regulates Synaptic Vesicle Clustering and Docking at a Vertebrate Synapse
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	article
author	Kaitlyn E. Fouke Kaitlyn E. Fouke M. Elizabeth Wegman Sarah A. Weber Sarah A. Weber Emily B. Brady Cristina Román-Vendrell Jennifer R. Morgan
author_facet	Kaitlyn E. Fouke Kaitlyn E. Fouke M. Elizabeth Wegman Sarah A. Weber Sarah A. Weber Emily B. Brady Cristina Román-Vendrell Jennifer R. Morgan
author_sort	Kaitlyn E. Fouke
title	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_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_sort	synuclein regulates synaptic vesicle clustering and docking at a vertebrate synapse
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/0886625b70a34663bc79bc0ace005b54
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_version_	1718405520719609856

Synuclein Regulates Synaptic Vesicle Clustering and Docking at a Vertebrate Synapse

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