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A mechanism of Munc18b–syntaxin 3–SANP25 complex assembly in regulated epithelial secretion
Author(s) -
Liu Ya,
Ding Xia,
Wang Dongmei,
Deng Hui,
Feng Mingye,
Wang Min,
Yu Xue,
Jiang Kai,
Ward Tarsha,
Aikhionbare Felix,
Guo Zhen,
Forte John G.,
Yao Xuebiao
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.07.083
Subject(s) - syntaxin , syntaxin 3 , snap25 , munc 18 , microbiology and biotechnology , exocytosis , secretion , snare complex , phosphorylation , chemistry , vesicle fusion , lipid bilayer fusion , biology , biochemistry , synaptic vesicle , vesicle , membrane
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.