Roles for Ca2+ mobilization and its regulation in mast cell functions: recent progress

Ca2+ mobilization in response to cross-linking of IgE bound to its high affinity receptor, FceRI, on mast cells is central to immune allergic responses. Stimulated tyrosine phosphorylation caused by this cross-linking activates store-operated Ca2+ entry that results in sustained Ca2+ oscillations dependent on Rho family GTPases and phosphoinositide synthesis. Coupling of the endoplasmic reticulum (ER) Ca2+ sensor, stromal interaction molecule 1 (STIM1), to the Ca2+-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 Ca2+ 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, Ca2+ 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. * CAD, : calcium activation domain; ER, : endoplasmic reticulum; PUFA, : polyunsaturated fatty acid; RBL, : rat basophilic leukaemia; RE, : recycling endosome; SOCE, : store-operated Ca2+ entry; STIM1, : stromal interaction molecule 1; TRPC, : transient receptor potential cation channel