Munc18/SNARE proteins’ regulation of exocytosis in guinea pig duodenal Brunner’s gland acini

作     者：Laura I Cosen-Binker Gerry P Morris Stephen Vanner Herbert Y Gaisano 

作者机构：Department of Medicine University of Toronto Toronto Ontario M5S 1A8 Canada Gastrointestinal Diseases Research Unit Queen's University Kingston Ontario KL7 5G2 Canada 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2008年第14卷第15期

页      面：2314-2322页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：Grants to H.Y.G. from the U.S. National Institute of Health  R21 AA015579-01A1 and to S.V. form the Canadian Institute of Health Research 

主　　题：胞吐作用 腺核 十二指肠 蛋白质调节 

摘      要：AIM: To examine the molecular mechanism of exocytosis in the Brunner’s gland acinar cell. METHODS: We used a submucosal preparation of guinea pig duodenal Brunner’s gland acini to visualize the dilation of the ductal lumen in response to cholinergic stimulus. We correlated this to electron microscopy to determine the extent of exocytosis of the mucin-filled vesicles. We then examined the behavior of SNARE and interacting Munc18 proteins by confocal microscopy. RESULTS: One and 6 μmol/L carbachol evoked a dose- dependent dilation of Brunner’s gland acini lumen, which correlated to the massive exocytosis of mucin. Munc18c and its cognate SNARE proteins Syntaxin-4 and SNAP-23 were localized to the apical plasma membrane, and upon cholinergic stimulation, Munc18c was displaced into the cytosol leaving Syntaxin-4 and SNAP-23 intact. CONCLUSION: Physiologic cholinergic stimulation induces Munc18c displacement from the Brunner’s gland acinar apical plasma membrane, which enables apical membrane Syntaxin-4 and SNAP-23 to form a SNARE complex with mucin-filled vesicle SNARE proteins to affect exocytosis.