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Munc18‐1 mutations that strongly impair SNARE‐complex binding support normal synaptic transmission
Author(s) -
Meijer Marieke,
Burkhardt Pawel,
de Wit Heidi,
Toonen Ruud F,
Fasshauer Dirk,
Verhage Matthijs
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.72
Subject(s) - biology , neurotransmission , synaptic vesicle , synaptic plasticity , neuroscience , lipid bilayer fusion , microbiology and biotechnology , snare complex , genetics , vesicle , receptor , membrane
Synaptic transmission depends critically on the Sec1p/Munc18 protein Munc18‐1, but it is unclear whether Munc18‐1 primarily operates as a integral part of the fusion machinery or has a more upstream role in fusion complex assembly. Here, we show that point mutations in Munc18‐1 that interfere with binding to the free Syntaxin1a N‐terminus and strongly impair binding to assembled SNARE complexes all support normal docking, priming and fusion of synaptic vesicles, and normal synaptic plasticity in munc18‐1 null mutant neurons. These data support a prevailing role of Munc18‐1 before/during SNARE‐complex assembly, while its continued association to assembled SNARE complexes is dispensable for synaptic transmission.