Reexamination of N-terminal domains of syntaxin-1 in vesicle fusion from central murine synapses
Syntaxin-1 (STX1) and Munc18-1 are two requisite components of synaptic vesicular release machinery, so much so synaptic transmission cannot proceed in their absence. They form a tight complex through two major binding modes: through STX1’s N-peptide and through STX1’s closed conformation driven by...
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eLife Sciences Publications Ltd
2021
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oai:doaj.org-article:55b4807767164058a2892123920a2a742021-11-29T12:45:51ZReexamination of N-terminal domains of syntaxin-1 in vesicle fusion from central murine synapses10.7554/eLife.694982050-084Xe69498https://doaj.org/article/55b4807767164058a2892123920a2a742021-08-01T00:00:00Zhttps://elifesciences.org/articles/69498https://doaj.org/toc/2050-084XSyntaxin-1 (STX1) and Munc18-1 are two requisite components of synaptic vesicular release machinery, so much so synaptic transmission cannot proceed in their absence. They form a tight complex through two major binding modes: through STX1’s N-peptide and through STX1’s closed conformation driven by its Habc- domain. However, physiological roles of these two reportedly different binding modes in synapses are still controversial. Here we characterized the roles of STX1’s N-peptide, Habc-domain, and open conformation with and without N-peptide deletion using our STX1-null mouse model system and exogenous reintroduction of STX1A mutants. We show, on the contrary to the general view, that the Habc-domain is absolutely required and N-peptide is dispensable for synaptic transmission. However, STX1A’s N-peptide plays a regulatory role, particularly in the Ca2+-sensitivity and the short-term plasticity of vesicular release, whereas STX1’s open conformation governs the vesicle fusogenicity. Strikingly, we also show neurotransmitter release still proceeds when the two interaction modes between STX1A and Munc18-1 are presumably intervened, necessitating a refinement of the conceptualization of STX1A–Munc18-1 interaction.Gülçin VardarAndrea Salazar-LázaroMarisa BrockmannMarion Weber-BoyvatSina ZobelVictor Wumbor-Apin KumbolThorsten TrimbuchChristian RosenmundeLife Sciences Publications Ltdarticlesyntaxin-1Munc18-1N-peptidehabc-domainleopen conformationsynaptic transmissionMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
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syntaxin-1 Munc18-1 N-peptide habc-domain leopen conformation synaptic transmission Medicine R Science Q Biology (General) QH301-705.5 |
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syntaxin-1 Munc18-1 N-peptide habc-domain leopen conformation synaptic transmission Medicine R Science Q Biology (General) QH301-705.5 Gülçin Vardar Andrea Salazar-Lázaro Marisa Brockmann Marion Weber-Boyvat Sina Zobel Victor Wumbor-Apin Kumbol Thorsten Trimbuch Christian Rosenmund Reexamination of N-terminal domains of syntaxin-1 in vesicle fusion from central murine synapses |
description |
Syntaxin-1 (STX1) and Munc18-1 are two requisite components of synaptic vesicular release machinery, so much so synaptic transmission cannot proceed in their absence. They form a tight complex through two major binding modes: through STX1’s N-peptide and through STX1’s closed conformation driven by its Habc- domain. However, physiological roles of these two reportedly different binding modes in synapses are still controversial. Here we characterized the roles of STX1’s N-peptide, Habc-domain, and open conformation with and without N-peptide deletion using our STX1-null mouse model system and exogenous reintroduction of STX1A mutants. We show, on the contrary to the general view, that the Habc-domain is absolutely required and N-peptide is dispensable for synaptic transmission. However, STX1A’s N-peptide plays a regulatory role, particularly in the Ca2+-sensitivity and the short-term plasticity of vesicular release, whereas STX1’s open conformation governs the vesicle fusogenicity. Strikingly, we also show neurotransmitter release still proceeds when the two interaction modes between STX1A and Munc18-1 are presumably intervened, necessitating a refinement of the conceptualization of STX1A–Munc18-1 interaction. |
format |
article |
author |
Gülçin Vardar Andrea Salazar-Lázaro Marisa Brockmann Marion Weber-Boyvat Sina Zobel Victor Wumbor-Apin Kumbol Thorsten Trimbuch Christian Rosenmund |
author_facet |
Gülçin Vardar Andrea Salazar-Lázaro Marisa Brockmann Marion Weber-Boyvat Sina Zobel Victor Wumbor-Apin Kumbol Thorsten Trimbuch Christian Rosenmund |
author_sort |
Gülçin Vardar |
title |
Reexamination of N-terminal domains of syntaxin-1 in vesicle fusion from central murine synapses |
title_short |
Reexamination of N-terminal domains of syntaxin-1 in vesicle fusion from central murine synapses |
title_full |
Reexamination of N-terminal domains of syntaxin-1 in vesicle fusion from central murine synapses |
title_fullStr |
Reexamination of N-terminal domains of syntaxin-1 in vesicle fusion from central murine synapses |
title_full_unstemmed |
Reexamination of N-terminal domains of syntaxin-1 in vesicle fusion from central murine synapses |
title_sort |
reexamination of n-terminal domains of syntaxin-1 in vesicle fusion from central murine synapses |
publisher |
eLife Sciences Publications Ltd |
publishDate |
2021 |
url |
https://doaj.org/article/55b4807767164058a2892123920a2a74 |
work_keys_str_mv |
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1718407343534768128 |