A role of VAMP8/endobrevin in regulated exocytosis of pancreatic acinar cells.
Dev Cell
; 7(3): 359-71, 2004 Sep.
Article
em En
| MEDLINE
| ID: mdl-15363411
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Pâncreas
/
Proteínas de Membrana
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article