Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice
Standard
Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice. / Hoffmann-Conaway, Sheila; Brockmann, Marisa M; Schneider, Katharina; Annamneedi, Anil; Rahman, Kazi Atikur; Bruns, Christine; Textoris-Taube, Kathrin; Trimbuch, Thorsten; Smalla, Karl-Heinz; Rosenmund, Christian; Gundelfinger, Eckart D; Garner, Craig Curtis; Montenegro-Venegas, Carolina.
In: ELIFE, Vol. 9, e56590, 04.05.2020.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice
AU - Hoffmann-Conaway, Sheila
AU - Brockmann, Marisa M
AU - Schneider, Katharina
AU - Annamneedi, Anil
AU - Rahman, Kazi Atikur
AU - Bruns, Christine
AU - Textoris-Taube, Kathrin
AU - Trimbuch, Thorsten
AU - Smalla, Karl-Heinz
AU - Rosenmund, Christian
AU - Gundelfinger, Eckart D
AU - Garner, Craig Curtis
AU - Montenegro-Venegas, Carolina
PY - 2020/5/4
Y1 - 2020/5/4
N2 - 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.
AB - 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.
U2 - 10.7554/eLife.56590
DO - 10.7554/eLife.56590
M3 - SCORING: Journal article
VL - 9
JO - ELIFE
JF - ELIFE
SN - 2050-084X
M1 - e56590
ER -