Mechanism of arachidonic acid action on syntaxin-Munc18

被引：73

作者：

Connell, Emma ^{[1
]}

Darios, Frederic ^{[1
]}

Broersen, Kerensa ^{[1
]}

Gatsby, Naomi ^{[1
]}

Peak-Chew, Sew-Yeu ^{[1
]}

Rickman, Colin ^{[1
]}

Davletov, Bazbek ^{[1
]}

机构：

[1] MRC, Mol Biol Lab, Cambridge CB2 2QH, England

来源：

EMBO REPORTS | 2007年 / 8卷 / 04期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1038/sj.embor.7400935

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：414 / 419

页数：6

共 32 条

[1] Promiscuous interaction of SNAP-25 with all plasma membrane syntaxins in a neuroendocrine cell [J].