Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice
Sheila Hoffmann-Conaway, Marisa M. Brockmann, Katharina Schneider, Anil Annamneedi, Kazi Atikur Rahman, Christine Bruns, Kathrin Textoris‐Taube, Thorsten Trimbuch, Karl‐Heinz Smalla, Christian Rosenmund, Eckart D. Gundelfinger, Craig C. Garner, Carolina Montenegro‐Venegas
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.