| Literature DB >> 17716669 |
Ya Liu1, Xia Ding, Dongmei Wang, Hui Deng, Mingye Feng, Min Wang, Xue Yu, Kai Jiang, Tarsha Ward, Felix Aikhionbare, Zhen Guo, John G Forte, Xuebiao Yao.
Abstract
Syntaxin and Munc18 are essential for regulated exocytosis in all eukaryotes. It was shown that Munc18 inhibition of neuronal syntaxin 1 can be overcome by CDK5 phosphorylation, indicating that structural change disrupts the syntaxin-Munc18 interaction. Here, we show that this phosphorylation promotes the assembly of Munc18b-syntaxin 3-SNAP25 tripartite complex and membrane fusion machinery SNARE. Using siRNAs to screen for genes required for regulated epithelial secretion, we identified the requirements of CDK5 and Munc18b in cAMP-dependent gastric acid secretion. Biochemical characterization revealed that Munc18b bears a syntaxin 3-selective binding site located at its most C-terminal 53 amino acids. Significantly, the phosphorylation of Thr572 by CDK5 attenuates Munc18b-syntaxin 3 interaction and promotes formation of Munc18b-syntaxin 3-SNAP25 tripartite complex, leading to an assembly of functional Munc18b-syntaxin 3-SNAP25-VAMP2 membrane fusion machinery. Thus, our studies suggest a novel regulatory mechanism in which phosphorylation of Munc18b operates vesicle docking and fusion in regulated exocytosis.Entities:
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Year: 2007 PMID： 17716669 PMCID： PMC3690314 DOI： 10.1016/j.febslet.2007.07.083
Source DB: PubMed Journal: FEBS Lett ISSN： 0014-5793 Impact factor: 4.124