The secretory granule protein syncollin binds to syntaxin in a Ca2(+)-sensitive manner.
The membrane proteins synaptobrevin, syntaxin, and SNAP-25 form the core of a ubiquitous fusion machine that interacts with the soluble proteins NSF and alpha-SNAP. During regulated exocytosis, membrane fusion is usually strictly controlled by Ca2+ ions. However, the mechanism by which Ca2+ regulates exocytosis is still unclear. Here we show that the membranes of exocrine secretory granules contain an 18-kDa protein, syncollin, that binds to syntaxin at low Ca2+ concentrations and dissociates at concentrations known to stimulate exocytosis. Syncollin has a single hydrophobic domain at its N-terminus and shows no significant homology with any known protein. Recombinant syncollin inhibits fusion in vitro between zymogen granules and pancreatic plasma membranes, and its potency falls as Ca2+ concentration rises. We suggest that syncollin acts as a Ca2(+)-sensitive regulator of exocytosis in exocrine tissues.
Edwardson
J M
JM
Department of Pharmacology, University of Cambridge, United Kingdom.
An
S
S
Jahn
R
R
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D003001:Cloning, Molecular; D003594:Cytoplasmic Granules / Q000737:chemistry* / Q000378:metabolism; D003902:Detergents; D004792:Enzyme Precursors / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology; D007536:Isomerism; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D017830:Octoxynol; D011485:Protein Binding / Q000187:drug effects; D050765:Qa-SNARE Proteins; D051381:Rats
D002352:Carrier Proteins; D003902:Detergents; D004792:Enzyme Precursors; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; C107454:Sycn protein, rat; D017830:Octoxynol; D002118:Calcium