| First Author | Hoffmann-Conaway S | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 32364493 | Mgi Jnum | J:290286 |
| Mgi Id | MGI:6442372 | Doi | 10.7554/eLife.56590 |
| Citation | Hoffmann-Conaway S, et al. (2020) Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice. Elife 9:e56590 |
| abstractText | 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. |
