A role of VAMP8/endobrevin in regulated exocytosis of pancreatic acinar cells.
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.
Pubmed ID: 15363411 RIS Download
Amylases | Animals | Blotting, Western | Carrier Proteins | Cell Division | Cells, Cultured | Endocytosis | Exocytosis | Fibroblasts | Genotype | Glutathione Transferase | Immunohistochemistry | Liver | Membrane Proteins | Mice | Mice, Knockout | Mice, Transgenic | Microscopy, Fluorescence | Models, Genetic | Pancreas | Pancreatitis | Precipitin Tests | Qa-SNARE Proteins | Qb-SNARE Proteins | Qc-SNARE Proteins | R-SNARE Proteins | SNARE Proteins | Time Factors | Vesicular Transport Proteins