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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Main Authors: Rajit Rajappa, Anne Gauthier-Kemper, Daniel Böning, Jana Hüve, Jürgen Klingauf
Format: Article
Language:English
Published: Elsevier 2016-02-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124716000528
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spelling 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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