Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice
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
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.
Reviewing Editor
- Eunjoon Kim, Institute for Basic Science, Korea Advanced Institute of Science and Technology, Republic of Korea
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).
Version history
- Received: March 3, 2020
- Accepted: May 2, 2020
- Accepted Manuscript published: May 4, 2020 (version 1)
- Version of Record published: May 14, 2020 (version 2)
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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