Synaptophysin 1 Clears Synaptobrevin 2 from the Presynaptic Active Zone to Prevent Short-Term Depression
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 mecha...
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doaj-01218ba8671f40aab6a0c83e728008d72020-11-24T22:14:29ZengElsevierCell Reports2211-12472016-02-011461369138110.1016/j.celrep.2016.01.031Synaptophysin 1 Clears Synaptobrevin 2 from the Presynaptic Active Zone to Prevent Short-Term DepressionRajit Rajappa0Anne Gauthier-Kemper1Daniel Böning2Jana Hüve3Jürgen Klingauf4Department of Cellular Biophysics, Institute of Medical Physics and Biophysics, University of Münster, 48149 Münster, GermanyDepartment of Cellular Biophysics, Institute of Medical Physics and Biophysics, University of Münster, 48149 Münster, GermanyDepartment of Cellular Biophysics, Institute of Medical Physics and Biophysics, University of Münster, 48149 Münster, GermanyDepartment of Cellular Biophysics, Institute of Medical Physics and Biophysics, University of Münster, 48149 Münster, GermanyDepartment of Cellular Biophysics, Institute of Medical Physics and Biophysics, University of Münster, 48149 Münster, GermanyRelease 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 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 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.http://www.sciencedirect.com/science/article/pii/S2211124716000528 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rajit Rajappa Anne Gauthier-Kemper Daniel Böning Jana Hüve Jürgen Klingauf |
spellingShingle |
Rajit Rajappa Anne Gauthier-Kemper Daniel Böning Jana Hüve Jürgen Klingauf Synaptophysin 1 Clears Synaptobrevin 2 from the Presynaptic Active Zone to Prevent Short-Term Depression Cell Reports |
author_facet |
Rajit Rajappa Anne Gauthier-Kemper Daniel Böning Jana Hüve Jürgen Klingauf |
author_sort |
Rajit Rajappa |
title |
Synaptophysin 1 Clears Synaptobrevin 2 from the Presynaptic Active Zone to Prevent Short-Term Depression |
title_short |
Synaptophysin 1 Clears Synaptobrevin 2 from the Presynaptic Active Zone to Prevent Short-Term Depression |
title_full |
Synaptophysin 1 Clears Synaptobrevin 2 from the Presynaptic Active Zone to Prevent Short-Term Depression |
title_fullStr |
Synaptophysin 1 Clears Synaptobrevin 2 from the Presynaptic Active Zone to Prevent Short-Term Depression |
title_full_unstemmed |
Synaptophysin 1 Clears Synaptobrevin 2 from the Presynaptic Active Zone to Prevent Short-Term Depression |
title_sort |
synaptophysin 1 clears synaptobrevin 2 from the presynaptic active zone to prevent short-term depression |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2016-02-01 |
description |
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 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 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. |
url |
http://www.sciencedirect.com/science/article/pii/S2211124716000528 |
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