A mechanism of Munc18b-syntaxin 3-SANP25 complex assembly in regulated epithelial secretion

作者：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^*

来源：FEBS LETTERS, 2007, 581(22): 4318-4324.

DOI：10.1016/j.febslet.2007.07.083

• SNARE
• syntaxin 3
• Munc18b
• CDK5
• exocytosis

Syntaxin and Munc18 are essential for regulated exocytosis in all eukaryotes. It was shown that Munc18 inhibition of neuronal syntaxin I 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-SNAP25VAMP2 membrane fusion machinery. Thus, our studies suggest a novel regulatory mechanism in which phosphorylation of Munc18b operates vesicle docking and fusion in regulated exocytosis.

• 出版日期2007-9-4
• 单位北京中医药大学; 中国科学技术大学