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Axonal transport of Hrs is activity dependent and facilitates synaptic vesicle protein degradation
Turnover of synaptic vesicle (SV) proteins is vital for the maintenance of healthy and functional synapses. SV protein turnover is driven by neuronal activity in an endosomal sorting complex required for transport (ESCRT)-dependent manner. Here, we characterize a critical step in this process: axona...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152131/ https://www.ncbi.nlm.nih.gov/pubmed/35636965 http://dx.doi.org/10.26508/lsa.202000745 |
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author | Birdsall, Veronica Kirwan, Konner Zhu, Mei Imoto, Yuuta Wilson, Scott M Watanabe, Shigeki Waites, Clarissa L |
author_facet | Birdsall, Veronica Kirwan, Konner Zhu, Mei Imoto, Yuuta Wilson, Scott M Watanabe, Shigeki Waites, Clarissa L |
author_sort | Birdsall, Veronica |
collection | PubMed |
description | Turnover of synaptic vesicle (SV) proteins is vital for the maintenance of healthy and functional synapses. SV protein turnover is driven by neuronal activity in an endosomal sorting complex required for transport (ESCRT)-dependent manner. Here, we characterize a critical step in this process: axonal transport of ESCRT-0 component Hrs, necessary for sorting proteins into the ESCRT pathway and recruiting downstream ESCRT machinery to catalyze multivesicular body (MVB) formation. We find that neuronal activity stimulates the formation of presynaptic endosomes and MVBs, as well as the motility of Hrs+ vesicles in axons and their delivery to SV pools. Hrs+ vesicles co-transport ESCRT-0 component STAM1 and comprise a subset of Rab5+ vesicles, likely representing pro-degradative early endosomes. Furthermore, we identify kinesin motor protein KIF13A as essential for the activity-dependent transport of Hrs to SV pools and the degradation of SV membrane proteins. Together, these data demonstrate a novel activity- and KIF13A-dependent mechanism for mobilizing axonal transport of ESCRT machinery to facilitate the degradation of SV membrane proteins. |
format | Online Article Text |
id | pubmed-9152131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-91521312022-06-13 Axonal transport of Hrs is activity dependent and facilitates synaptic vesicle protein degradation Birdsall, Veronica Kirwan, Konner Zhu, Mei Imoto, Yuuta Wilson, Scott M Watanabe, Shigeki Waites, Clarissa L Life Sci Alliance Research Articles Turnover of synaptic vesicle (SV) proteins is vital for the maintenance of healthy and functional synapses. SV protein turnover is driven by neuronal activity in an endosomal sorting complex required for transport (ESCRT)-dependent manner. Here, we characterize a critical step in this process: axonal transport of ESCRT-0 component Hrs, necessary for sorting proteins into the ESCRT pathway and recruiting downstream ESCRT machinery to catalyze multivesicular body (MVB) formation. We find that neuronal activity stimulates the formation of presynaptic endosomes and MVBs, as well as the motility of Hrs+ vesicles in axons and their delivery to SV pools. Hrs+ vesicles co-transport ESCRT-0 component STAM1 and comprise a subset of Rab5+ vesicles, likely representing pro-degradative early endosomes. Furthermore, we identify kinesin motor protein KIF13A as essential for the activity-dependent transport of Hrs to SV pools and the degradation of SV membrane proteins. Together, these data demonstrate a novel activity- and KIF13A-dependent mechanism for mobilizing axonal transport of ESCRT machinery to facilitate the degradation of SV membrane proteins. Life Science Alliance LLC 2022-05-30 /pmc/articles/PMC9152131/ /pubmed/35636965 http://dx.doi.org/10.26508/lsa.202000745 Text en © 2022 Birdsall et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Birdsall, Veronica Kirwan, Konner Zhu, Mei Imoto, Yuuta Wilson, Scott M Watanabe, Shigeki Waites, Clarissa L Axonal transport of Hrs is activity dependent and facilitates synaptic vesicle protein degradation |
title | Axonal transport of Hrs is activity dependent and facilitates synaptic vesicle protein degradation |
title_full | Axonal transport of Hrs is activity dependent and facilitates synaptic vesicle protein degradation |
title_fullStr | Axonal transport of Hrs is activity dependent and facilitates synaptic vesicle protein degradation |
title_full_unstemmed | Axonal transport of Hrs is activity dependent and facilitates synaptic vesicle protein degradation |
title_short | Axonal transport of Hrs is activity dependent and facilitates synaptic vesicle protein degradation |
title_sort | axonal transport of hrs is activity dependent and facilitates synaptic vesicle protein degradation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152131/ https://www.ncbi.nlm.nih.gov/pubmed/35636965 http://dx.doi.org/10.26508/lsa.202000745 |
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