Phosphorylation of SNAP-23 regulates exocytosis from mast cells.

TitlePhosphorylation of SNAP-23 regulates exocytosis from mast cells.
Publication TypeJournal Article
Year of Publication2005
JournalThe Journal of biological chemistry
Volume280
Issue8
Pagination6610-20
Date Published2005 Feb 25
ISSN0021-9258
AbstractRegulated exocytosis is a process in which a physiological trigger initiates the translocation, docking, and fusion of secretory granules with the plasma membrane. A class of proteins termed SNAREs (including SNAP-23, syntaxins, and VAMPs) are known regulators of secretory granule/plasma membrane fusion events. We have investigated the molecular mechanisms of regulated exocytosis in mast cells and find that SNAP-23 is phosphorylated when rat basophilic leukemia mast cells are triggered to degranulate. The kinetics of SNAP-23 phosphorylation mirror the kinetics of exocytosis. We have identified amino acid residues Ser(95) and Ser(120) as the major phosphorylation sites in SNAP-23 in rodent mast cells. Quantitative analysis revealed that approximately 10% of SNAP-23 was phosphorylated when mast cell degranulation was induced. These same residues were phosphorylated when mouse platelet degranulation was induced with thrombin, demonstrating that phosphorylation of SNAP-23 Ser(95) and Ser(120) is not restricted to mast cells. Although triggering exocytosis did not alter the absolute amount of SNAP-23 bound to SNAREs, after stimulation essentially all of the SNAP-23 bound to the plasma membrane SNARE syntaxin 4 and the vesicle SNARE VAMP-2 was phosphorylated. Regulated exocytosis studies revealed that overexpression of SNAP-23 phosphorylation mutants inhibited exocytosis from rat basophilic leukemia mast cells, demonstrating that phosphorylation of SNAP-23 on Ser(120) and Ser(95) modulates regulated exocytosis by mast cells.
URLhttp://www.jbc.org/cgi/pmidlookup?view=long&pmid=15611044
DOI10.1074/jbc.M412126200
PubMed Linkhttp://www.ncbi.nlm.nih.gov/pubmed/15611044?dopt=Abstract
Short TitleJ Biol Chem