Synaptophysin 1 Clears Synaptobrevin 2 from the Presynaptic Active Zone to Prevent Short-Term Depression

Synaptophysin 1 Clears Synaptobrevin 2 from the Presynaptic Active Zone to Prevent Short-Term Depression

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Release site clearance is an important process during synaptic vesicle (SV) recycling.However, little is known about its molecular mechanism.Here we identify self-assembly of exocytosed Synaptobrevin 2 (Syb2) and Synaptophysin 1 (Syp1) by homo- and hetero-oligomerization into clusters as key mechanisms mediating release site clearance for glitter foam vellen action preventing cis-SNARE complex formation at the active zone (AZ).In hippocampal neurons from Syp1 knockout mice, neurons expressing a monomeric Syb2 mutant, or after acute block of the ATPase N-ethylmaleimide-sensitive factor (NSF), responsible for cis-SNARE complex disassembly, we found strong frequency-dependent short-term depression (STD), whereas retrieval of Syb2 by compensatory endocytosis was only affected weakly.Defects in Syb2 endocytosis were stimulus- and frequency-dependent, indicating that here Syp1 is not essential for Syb2 retrieval, but for its efficient clearance upstream of endocytosis.

Our findings identify an SV protein as a release site clearance factor.