Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice
- German Center for Neurodegenerative Diseases, Germany
- Charité - Universitätsmedizin Berlin, Germany
- Leibniz Institute for Neurobiology, Germany
Abstract
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.
Data availability
All data generated or analysed during this study are included in the manuscript.
Article and author information
Author details
Marisa M Brockmann
Kazi Atikur Rahman
Christian Rosenmund
Craig Curtis Garner
Funding
Federal Government of Germany (SFB958)
- Craig Curtis Garner
Federal Government of Germany (SFB779/B09)
- Eckart D Gundelfinger
BMBF (20150065)
- Eckart D Gundelfinger
BMBF (20150065)
- Karl-Heinz Smalla
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Breeding of animals and experiments using animal material were carried out in accordance with the European Communities Council Directive (2010/63/EU) and approved by the local animal care committees of Sachsen-Anhalt or the animal welfare committee of Charité Medical University and the Berlin state government (protocol number: T0036/14, O0208/16).
Copyright
© 2020, Hoffmann-Conaway et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice
eLife 9:e56590.
https://doi.org/10.7554/eLife.56590
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