Identification of SNAREs that mediate zymogen granule exocytosis.
A secretagogue-stimulated pancreatic acinar cell releases digestive enzymes from its apical pole. We attempted to identify the SNAREs involved in zymogen granule exocytosis. Antibodies against syntaxins 2 and 3, SNAP-23 and VAMP 8, and the corresponding recombinant SNAREs, inhibited amylase secretion from streptolysin O-permeabilised acini; other anti-SNARE antibodies and SNAREs had no effect. Botulinum neurotoxin C, which cleaved syntaxin 2 and (to a lesser extent) syntaxin 3, but not syntaxins 4, 7 or 8, also inhibited exocytosis. We propose that syntaxin 2, SNAP-23 and VAMP 8 mediate primary granule-plasma membrane fusion. Syntaxin 3 may be involved in secondary granule-granule fusion.
Pickett
James A
JA
Department of Pharmacology, Tennis Court Road, University of Cambridge, Cambridge CB2 1PD, UK.
Campos-Toimil
Manuel
M
Thomas
Paul
P
Edwardson
J Michael
JM
D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D002478:Cells, Cultured; D004792:Enzyme Precursors / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects; D051381:Rats; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism*
D004792:Enzyme Precursors; D050600:SNARE Proteins; D001905:Botulinum Toxins; C096324:botulinum toxin type C