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The synaptic vesicle SNARE neuronal Synaptobrevin promotes endolysosomal degradation and prevents neurodegeneration

Soluble NSF attachment protein receptors (SNAREs) are the core proteins in membrane fusion. The neuron-specific synaptic v-SNARE n-syb (neuronal Synaptobrevin) plays a key role during synaptic vesicle exocytosis. In this paper, we report that loss of n-syb caused slow neurodegeneration independent o...

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Autores principales: Haberman, Adam, Williamson, W. Ryan, Epstein, Daniel, Wang, Dong, Rina, Srisha, Meinertzhagen, Ian A., Hiesinger, P. Robin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265959/
https://www.ncbi.nlm.nih.gov/pubmed/22270918
http://dx.doi.org/10.1083/jcb.201108088
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author Haberman, Adam
Williamson, W. Ryan
Epstein, Daniel
Wang, Dong
Rina, Srisha
Meinertzhagen, Ian A.
Hiesinger, P. Robin
author_facet Haberman, Adam
Williamson, W. Ryan
Epstein, Daniel
Wang, Dong
Rina, Srisha
Meinertzhagen, Ian A.
Hiesinger, P. Robin
author_sort Haberman, Adam
collection PubMed
description Soluble NSF attachment protein receptors (SNAREs) are the core proteins in membrane fusion. The neuron-specific synaptic v-SNARE n-syb (neuronal Synaptobrevin) plays a key role during synaptic vesicle exocytosis. In this paper, we report that loss of n-syb caused slow neurodegeneration independent of its role in neurotransmitter release in adult Drosophila melanogaster photoreceptor neurons. In addition to synaptic vesicles, n-Syb localized to endosomal vesicles. Loss of n-syb lead to endosomal accumulations, transmembrane protein degradation defects, and a secondary increase in autophagy. Our evidence suggests a primary defect of impaired delivery of vesicles that contain degradation proteins, including the acidification-activated Cathepsin proteases and the neuron-specific proton pump and V0 adenosine triphosphatase component V100. Overexpressing V100 partially rescued n-syb–dependent degeneration through an acidification-independent endosomal sorting mechanism. Collectively, these findings reveal a role for n-Syb in a neuron-specific sort-and-degrade mechanism that protects neurons from degeneration. Our findings further shed light on which intraneuronal compartments exhibit increased or decreased neurotoxicity.
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spelling pubmed-32659592012-07-23 The synaptic vesicle SNARE neuronal Synaptobrevin promotes endolysosomal degradation and prevents neurodegeneration Haberman, Adam Williamson, W. Ryan Epstein, Daniel Wang, Dong Rina, Srisha Meinertzhagen, Ian A. Hiesinger, P. Robin J Cell Biol Research Articles Soluble NSF attachment protein receptors (SNAREs) are the core proteins in membrane fusion. The neuron-specific synaptic v-SNARE n-syb (neuronal Synaptobrevin) plays a key role during synaptic vesicle exocytosis. In this paper, we report that loss of n-syb caused slow neurodegeneration independent of its role in neurotransmitter release in adult Drosophila melanogaster photoreceptor neurons. In addition to synaptic vesicles, n-Syb localized to endosomal vesicles. Loss of n-syb lead to endosomal accumulations, transmembrane protein degradation defects, and a secondary increase in autophagy. Our evidence suggests a primary defect of impaired delivery of vesicles that contain degradation proteins, including the acidification-activated Cathepsin proteases and the neuron-specific proton pump and V0 adenosine triphosphatase component V100. Overexpressing V100 partially rescued n-syb–dependent degeneration through an acidification-independent endosomal sorting mechanism. Collectively, these findings reveal a role for n-Syb in a neuron-specific sort-and-degrade mechanism that protects neurons from degeneration. Our findings further shed light on which intraneuronal compartments exhibit increased or decreased neurotoxicity. The Rockefeller University Press 2012-01-23 /pmc/articles/PMC3265959/ /pubmed/22270918 http://dx.doi.org/10.1083/jcb.201108088 Text en © 2012 Haberman et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Haberman, Adam
Williamson, W. Ryan
Epstein, Daniel
Wang, Dong
Rina, Srisha
Meinertzhagen, Ian A.
Hiesinger, P. Robin
The synaptic vesicle SNARE neuronal Synaptobrevin promotes endolysosomal degradation and prevents neurodegeneration
title The synaptic vesicle SNARE neuronal Synaptobrevin promotes endolysosomal degradation and prevents neurodegeneration
title_full The synaptic vesicle SNARE neuronal Synaptobrevin promotes endolysosomal degradation and prevents neurodegeneration
title_fullStr The synaptic vesicle SNARE neuronal Synaptobrevin promotes endolysosomal degradation and prevents neurodegeneration
title_full_unstemmed The synaptic vesicle SNARE neuronal Synaptobrevin promotes endolysosomal degradation and prevents neurodegeneration
title_short The synaptic vesicle SNARE neuronal Synaptobrevin promotes endolysosomal degradation and prevents neurodegeneration
title_sort synaptic vesicle snare neuronal synaptobrevin promotes endolysosomal degradation and prevents neurodegeneration
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265959/
https://www.ncbi.nlm.nih.gov/pubmed/22270918
http://dx.doi.org/10.1083/jcb.201108088
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