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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
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.
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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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