A role of VAMP8/endobrevin in regulated exocytosis of pancreatic acinar cells

被引：136

作者：

Wang, CC ^{[1
]}

Ng, CP ^{[1
]}

Lu, L ^{[1
]}

Atlashkin, V ^{[1
]}

Zhang, W ^{[1
]}

Seet, LF ^{[1
]}

Hong, WJ ^{[1
]}

机构：

[1] Inst Mol & Cell Biol, Membrane Biol Lab, Singapore 138673, Singapore

来源：

DEVELOPMENTAL CELL | 2004年 / 7卷 / 03期

关键词：

D O I：

10.1016/j.devcel.2004.08.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Despite our general understanding that members of the SNARE superfamily participate in diverse intracellular docking/fusion events, the physiological role of the majority of SNAREs in the intact organism remains elusive. In this study, through targeted gene knockout in mice, we establish that VAMP8/endobrevin is a major player in regulated exocytosis of the exocrine pancreas. VAMP8 is enriched on the membrane of zymogen granules and exists in a complex with syntaxin 4 and SNAP-23. VAMP8(-/-) mice developed normally but showed severe defects in the pancreas. VAMP8 null acinar cells contained three times more zymogen granules than control acinar cells. Furthermore, secretagogue-stimulated secretion was abolished in pancreatic fragments derived from VAMP8(-/-) mice. In addition, VAMP8(-/-) mice were partially resistant to supramaximal caerulein-induced pancreatitis. These results suggest a major physiological role of VAMP8 in regulated exocytosis of pancreatic acinar cells by serving as a v-SNARE of zymogen granules.

引用

页码：359 / 371

页数：13

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