1. Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice
- Author
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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 Curtis Garner, and Carolina Montenegro-Venegas
- Subjects
Male ,genetics [Synaptic Vesicles] ,Mouse ,Vesicle-Associated Membrane Protein 2 ,E3 ubiquitin ligases ,Hippocampus ,parkin ,ultrastructure [Hippocampus] ,Biology (General) ,Cells, Cultured ,genetics [Nerve Tissue Proteins] ,presynapse ,Mice, Knockout ,genetics [Ubiquitin-Protein Ligases] ,Membrane Glycoproteins ,metabolism [Vesicle-Associated Membrane Protein 2] ,ultrastructure [Presynaptic Terminals] ,enzymology [Synaptic Vesicles] ,Medicine ,Female ,Synaptic Vesicles ,Research Article ,Signal Transduction ,autophagy ,QH301-705.5 ,Ubiquitin-Protein Ligases ,Science ,Presynaptic Terminals ,Nerve Tissue Proteins ,ubiquitination ,enzymology [Presynaptic Terminals] ,ultrastructure [Synaptic Vesicles] ,enzymology [Hippocampus] ,metabolism [Ubiquitin-Protein Ligases] ,Autophagy ,Animals ,metabolism [Nerve Tissue Proteins] ,deficiency [Nerve Tissue Proteins] ,bassoon ,Ubiquitination ,Mice, Inbred C57BL ,Proteolysis ,Proteostasis ,mouse ,neuroscience ,ddc:600 ,metabolism [Membrane Glycoproteins] ,Neuroscience - 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.
- Published
- 2020
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