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.
Wang
Cheng-Chun
CC
Membrane Biology Laboratory, Institute of Molecular and Cell Biology, Proteos, 61 Biopolis Drive, Singapore 138673, Singapore.
Ng
Chee Peng
CP
Lu
Lei
L
Atlashkin
Vadim
V
Zhang
Wei
W
Seet
Li-Fong
LF
Hong
Wanjin
W
D000681:Amylases / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D004705:Endocytosis; D005089:Exocytosis; D005347:Fibroblasts / Q000378:metabolism; D005838:Genotype; D005982:Glutathione Transferase / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D010195:Pancreatitis / Q000378:metabolism; D011233:Precipitin Tests; D050765:Qa-SNARE Proteins; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D013997:Time Factors; D033921:Vesicular Transport Proteins / Q000378:metabolism
D002352:Carrier Proteins; D008565:Membrane Proteins; D050765:Qa-SNARE Proteins; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D050683:R-SNARE Proteins; C100493:SNAP23 protein, human; D050600:SNARE Proteins; C107017:Snap23 protein, mouse; C491831:Vamp8 protein, mouse; D033921:Vesicular Transport Proteins; D005982:Glutathione Transferase; D000681:Amylases