Syntaxin 3 is required for cAMP-induced acid secretion: streptolysin O-permeabilized gastric gland model

被引:44
作者
Ammar, DA [1 ]
Zhou, RH [1 ]
Forte, JG [1 ]
Yao, XB [1 ]
机构
[1] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2002年 / 282卷 / 01期
关键词
SNARE hypothesis; membrane fusion; ezrin; wortmannin; hydrogen; potassium-adenosinetriphosphatase;
D O I
10.1152/ajpgi.00277.2002
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Gastric gland stimulation triggers H+,K+-ATPase translocation from cytoplasmic tubulovesicles to apical plasma membrane in parietal cells, resulting in HCl secretion. We studied the mechanisms involved in tubulovesicle translocation with a permeabilized gland system. Streptolysin O (SLO)-treated glands were permeabilized such that exogenous fluorescently labeled actin incorporated into cytoskeleton in a pattern mimicking endogenous F-actin. As shown by accumulation of the weak base aminopyrine (AP), SLO-permeabilized glands are stimulated to secrete acid by addition of cAMP and ATP and inhibited by proton pump inhibitors. Direct visualization with the fluorescent pH probe Lysosensor showed acid accumulation in glandular lumen and parietal cell canaliculi. ME-3407, an antiulcer drug with inhibitory action implicated to involve ezrin, inhibited AP uptake in and effectively released ezrin from intact and SLO-permeabilized glands. In contrast, wortmannin, an effective secretion inhibitor in intact glands, had minimal effects on ezrin or AP accumulation in SLO-permeabilized glands. The finding that SNARE protein syntaxin 3 is associated with H+,K+-ATPase-containing tubulovesicles suggested that it is involved in membrane fusion. Addition of recombinant syntaxin 3, but not syntaxin 5 or heat-denatured syntaxin 3, dose-dependently inhibited acid secretion. Our studies are consistent with a membrane recycling hypothesis that activation of protein kinase cascades leads to SNARE-mediated fusion of H+,K+-ATPase-containing tubulovesicles to apical plasma membrane.
引用
收藏
页码:G23 / G33
页数:11
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