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Mechanism of arachidonic acid action on syntaxin–Munc18
Author(s) -
Connell Emma,
Darios Frédéric,
Broersen Kerensa,
Gatsby Naomi,
PeakChew SewYeu,
Rickman Colin,
Davletov Bazbek
Publication year - 2007
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400935
Subject(s) - syntaxin 3 , syntaxin , stx1a , microbiology and biotechnology , arachidonic acid , munc 18 , chemistry , exocytosis , biology , biochemistry , synaptic vesicle , vesicle , membrane , enzyme
Syntaxin and Munc18 are, in tandem, essential for exocytosis in all eukaryotes. Recently, it was shown that Munc18 inhibition of neuronal syntaxin 1 can be overcome by arachidonic acid, indicating that this common second messenger acts to disrupt the syntaxin–Munc18 interaction. Here, we show that arachidonic acid can stimulate syntaxin 1 alone, indicating that it is syntaxin 1 that undergoes a structural change in the syntaxin 1–Munc18 complex. Arachidonic acid is incapable of dissociating Munc18 from syntaxin 1 and, crucially, Munc18 remains associated with syntaxin 1 after arachidonic‐acid‐induced syntaxin 1 binding to synaptosomal‐associated protein 25 kDa (SNAP25). We also show that the same principle operates in the case of the ubiquitous syntaxin 3 isoform, highlighting the conserved nature of the mechanism of arachidonic acid action. Neuronal soluble N‐ethyl maleimide sensitive factor attachment protein receptors (SNAREs) can be isolated from brain membranes in a complex with endogenous Munc18, consistent with a proposed function of Munc18 in vesicle docking and fusion.