title: Roles for Ca2+ mobilization and its regulation in mast cell functions: recent progress.
abstract: Ca(2+)mobilization in response to cross-linking of IgE bound to its high affinity receptor, FcεRI, on mast cells is central to immune allergic responses. Stimulated tyrosine phosphorylation caused by this cross-linking activates store-operated Ca(2+)entry that results in sustained Ca(2+)oscillations dependent on Rho family GTPases and phosphoinositide synthesis. Coupling of the endoplasmic reticulum (ER) Ca(2+)sensor, stromal interaction molecule 1 (STIM1), to the Ca(2+)-selective channel, Orai1, is regulated by these elements and depends on membrane organization, both at the plasma membrane and at the ER. Mitochondria also contribute to the regulation of Ca(2+)mobilization, and we describe recent evidence that the ER membrane protein vesicle-associated membrane protein-associated protein (VAP) plays a significant role in the coupling between ER and mitochondria in this process. In addition to granule exocytosis, Ca(2+)mobilization in these cells also contributes to stimulated outward trafficking of recycling endosomes and to antigen-stimulated chemotaxis, and it is pathologically regulated by protozoan parasitic invasion.
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, U.S.A. dah24@cornell.edu.
authors.forename: David
authors.initials: D
authors.lastname: Holowka
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, U.S.A.
authors.forename: Marcus
authors.initials: M
authors.lastname: Wilkes
authors.affiliation: MRC Laboratory for Molecular Cell Biology, University College London, WC1E 6BT London, U.K.
authors.forename: Christopher
authors.initials: C
authors.lastname: Stefan
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, U.S.A.
authors.forename: Barbara
authors.initials: B
authors.lastname: Baird
mesh_terms: D002118:Calcium / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008407:Mast Cells / Q000166:cytology*; D009363:Neoplasm Proteins / Q000378:metabolism; D000071740:ORAI1 Protein / Q000378:metabolism; D000071737:Stromal Interaction Molecule 1 / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D002118:Calcium
keywords: IgE receptors; calcium mobilization; mast cells; mitochondrial–endoplasmic reticulum coupling; vesicle-associated membrane protein-associated protein (VAP)