Reexamination of N-terminal domains of syntaxin-1 in vesicle fusion from central murine synapses
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Reexamination of N-terminal domains of syntaxin-1 in vesicle fusion from central murine synapses. / Vardar, Gülçin; Salazar-Lázaro, Andrea; Brockmann, Marisa; Weber-Boyvat, Marion; Zobel, Sina; Kumbol, Victor Wumbor-Apin; Trimbuch, Thorsten; Rosenmund, Christian.
in: ELIFE, Jahrgang 10, 24.08.2021.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Reexamination of N-terminal domains of syntaxin-1 in vesicle fusion from central murine synapses
AU - Vardar, Gülçin
AU - Salazar-Lázaro, Andrea
AU - Brockmann, Marisa
AU - Weber-Boyvat, Marion
AU - Zobel, Sina
AU - Kumbol, Victor Wumbor-Apin
AU - Trimbuch, Thorsten
AU - Rosenmund, Christian
PY - 2021/8/24
Y1 - 2021/8/24
N2 - 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.
AB - 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.
UR - https://doi.org/10.7554/eLife.69498
U2 - 10.7554/eLife.69498
DO - 10.7554/eLife.69498
M3 - SCORING: Journal article
VL - 10
JO - ELIFE
JF - ELIFE
SN - 2050-084X
ER -
