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Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice
Mechanisms regulating the turnover of synaptic vesicle (SV) proteins are not well understood. They are thought to require poly-ubiquitination and degradation through proteasome, endo-lysosomal or autophagy-related pathways. Bassoon was shown to negatively regulate presynaptic autophagy in part by sc...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224700/ https://www.ncbi.nlm.nih.gov/pubmed/32364493 http://dx.doi.org/10.7554/eLife.56590 |
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author | Hoffmann-Conaway, Sheila Brockmann, Marisa M Schneider, Katharina Annamneedi, Anil Rahman, Kazi Atikur Bruns, Christine Textoris-Taube, Kathrin Trimbuch, Thorsten Smalla, Karl-Heinz Rosenmund, Christian Gundelfinger, Eckart D Garner, Craig Curtis Montenegro-Venegas, Carolina |
author_facet | Hoffmann-Conaway, Sheila Brockmann, Marisa M Schneider, Katharina Annamneedi, Anil Rahman, Kazi Atikur Bruns, Christine Textoris-Taube, Kathrin Trimbuch, Thorsten Smalla, Karl-Heinz Rosenmund, Christian Gundelfinger, Eckart D Garner, Craig Curtis Montenegro-Venegas, Carolina |
author_sort | Hoffmann-Conaway, Sheila |
collection | PubMed |
description | Mechanisms regulating the turnover of synaptic vesicle (SV) proteins are not well understood. They are thought to require poly-ubiquitination and degradation through proteasome, endo-lysosomal or autophagy-related pathways. Bassoon was shown to negatively regulate presynaptic autophagy in part by scaffolding Atg5. Here, we show that increased autophagy in Bassoon knockout neurons depends on poly-ubiquitination and that the loss of Bassoon leads to elevated levels of ubiquitinated synaptic proteins per se. Our data show that Bassoon knockout neurons have a smaller SV pool size and a higher turnover rate as indicated by a younger pool of SV2. The E3 ligase Parkin is required for increased autophagy in Bassoon-deficient neurons as the knockdown of Parkin normalized autophagy and SV protein levels and rescued impaired SV recycling. These data indicate that Bassoon is a key regulator of SV proteostasis and that Parkin is a key E3 ligase in the autophagy-mediated clearance of SV proteins. |
format | Online Article Text |
id | pubmed-7224700 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-72247002020-05-15 Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice Hoffmann-Conaway, Sheila Brockmann, Marisa M Schneider, Katharina Annamneedi, Anil Rahman, Kazi Atikur Bruns, Christine Textoris-Taube, Kathrin Trimbuch, Thorsten Smalla, Karl-Heinz Rosenmund, Christian Gundelfinger, Eckart D Garner, Craig Curtis Montenegro-Venegas, Carolina eLife Neuroscience Mechanisms regulating the turnover of synaptic vesicle (SV) proteins are not well understood. They are thought to require poly-ubiquitination and degradation through proteasome, endo-lysosomal or autophagy-related pathways. Bassoon was shown to negatively regulate presynaptic autophagy in part by scaffolding Atg5. Here, we show that increased autophagy in Bassoon knockout neurons depends on poly-ubiquitination and that the loss of Bassoon leads to elevated levels of ubiquitinated synaptic proteins per se. Our data show that Bassoon knockout neurons have a smaller SV pool size and a higher turnover rate as indicated by a younger pool of SV2. The E3 ligase Parkin is required for increased autophagy in Bassoon-deficient neurons as the knockdown of Parkin normalized autophagy and SV protein levels and rescued impaired SV recycling. These data indicate that Bassoon is a key regulator of SV proteostasis and that Parkin is a key E3 ligase in the autophagy-mediated clearance of SV proteins. eLife Sciences Publications, Ltd 2020-05-04 /pmc/articles/PMC7224700/ /pubmed/32364493 http://dx.doi.org/10.7554/eLife.56590 Text en © 2020, Hoffmann-Conaway et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Hoffmann-Conaway, Sheila Brockmann, Marisa M Schneider, Katharina Annamneedi, Anil Rahman, Kazi Atikur Bruns, Christine Textoris-Taube, Kathrin Trimbuch, Thorsten Smalla, Karl-Heinz Rosenmund, Christian Gundelfinger, Eckart D Garner, Craig Curtis Montenegro-Venegas, Carolina Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice |
title | Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice |
title_full | Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice |
title_fullStr | Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice |
title_full_unstemmed | Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice |
title_short | Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice |
title_sort | parkin contributes to synaptic vesicle autophagy in bassoon-deficient mice |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224700/ https://www.ncbi.nlm.nih.gov/pubmed/32364493 http://dx.doi.org/10.7554/eLife.56590 |
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