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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Gülçin Vardar, Andrea Salazar-Lázaro, Marisa Brockmann, Marion Weber-Boyvat, Sina Zobel, Victor Wumbor-Apin Kumbol, Thorsten Trimbuch, Christian Rosenmund
Formato: article
Lenguaje:EN
Publicado: eLife Sciences Publications Ltd 2021
Materias:
R
Q
Acceso en línea:https://doaj.org/article/55b4807767164058a2892123920a2a74
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:55b4807767164058a2892123920a2a74
record_format dspace
spelling 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)
institution DOAJ
collection DOAJ
language EN
topic syntaxin-1
Munc18-1
N-peptide
habc-domain
leopen conformation
synaptic transmission
Medicine
R
Science
Q
Biology (General)
QH301-705.5
spellingShingle 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 AT gulcinvardar reexaminationofnterminaldomainsofsyntaxin1invesiclefusionfromcentralmurinesynapses
AT andreasalazarlazaro reexaminationofnterminaldomainsofsyntaxin1invesiclefusionfromcentralmurinesynapses
AT marisabrockmann reexaminationofnterminaldomainsofsyntaxin1invesiclefusionfromcentralmurinesynapses
AT marionweberboyvat reexaminationofnterminaldomainsofsyntaxin1invesiclefusionfromcentralmurinesynapses
AT sinazobel reexaminationofnterminaldomainsofsyntaxin1invesiclefusionfromcentralmurinesynapses
AT victorwumborapinkumbol reexaminationofnterminaldomainsofsyntaxin1invesiclefusionfromcentralmurinesynapses
AT thorstentrimbuch reexaminationofnterminaldomainsofsyntaxin1invesiclefusionfromcentralmurinesynapses
AT christianrosenmund reexaminationofnterminaldomainsofsyntaxin1invesiclefusionfromcentralmurinesynapses
_version_ 1718407343534768128