Alcoholic chronic pancreatitis involves displacement of Munc18c from the pancreatic acinar basal membrane surface.
The minimal machinery for fusion of secretory vesicles with the cell membrane is a cognate set of v- and t-SNAREs on opposing membranes. Spontaneous SNARE complex assembly leading to unregulated membrane fusion is prevented by Munc18 proteins that bind membrane SNAREs syntaxins. Munc18 blocks syntaxin interactions with cognate SNARE proteins and thereby act as an inhibitor of exocytosis. The pancreatic acinar cell contains several sets of cognate SNAREs and Munc18 proteins that mediate the distinct exocytic events. We had reported that in the rat pancreas, Munc18c co-localizes with t-SNAREs syntaxin4 and SNAP23 on the acinar cell basolateral plasma membrane. Under conditions that induce pancreatitis in vivo, displacement of Munc18c from the basolateral plasma membrane relieved its blockade of SNARE-mediated membrane fusion in this region and thereby redirected apical exocytosis to the basal membrane surface. Here we show in a case of human mild alcoholic chronic pancreatitis that Munc18c is also displaced from the plasma membrane of intact acinar cells, which would render these cells receptive to pathologic basolateral exocytosis and further episodes of pancreatitis.
Gaisano
Herbert Y
HY
Department of Medicine, University of Toronto, Toronto, Ontario, Canada. herbert.gaisano@utoronto.ca
Sheu
Laura
L
Whitcomb
David
D
D002352:Carrier Proteins / Q000032:analysis; D002462:Cell Membrane / Q000737:chemistry*; D016764:Cell Polarity; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D010179:Pancreas / Q000737:chemistry* / Q000166:cytology / Q000473:pathology; D019512:Pancreatitis, Alcoholic / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000032:analysis*; D050765:Qa-SNARE Proteins; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D008565:Membrane Proteins; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D050765:Qa-SNARE Proteins; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; C100493:SNAP23 protein, human; D033921:Vesicular Transport Proteins