title: Emerging roles of store-operated Ca²⁺ entry through STIM and ORAI proteins in immunity, hemostasis and cancer.
abstract: Store-operated Ca(2+) entry (SOCE) is an important Ca(2+) influx pathway, which is defined by the fact that depletion of intracellular Ca(2+) stores, mainly the endoplasmic reticulum (ER), triggers the opening of Ca(2+) channels in the plasma membrane. The best characterized SOC channel is the Ca(2+) release-activated Ca(2+) (CRAC) channel, which was first described in cells of the immune system but has since been reported in many different cell types. CRAC channels are multimers of ORAI family proteins, of which ORAI1 is the best characterized. They are activated by stromal interaction molecules (STIM) 1 and 2, which respond to the depletion of intracellular Ca(2+) stores with oligomerization and binding to ORAI proteins. The resulting SOCE is critical for the physiological function of many cell types including immune cells and platelets. Recent studies using cell lines, animal models and primary cells from human patients with defects in SOCE have highlighted the importance of this Ca(2+) entry mechanism in a variety of pathophysiological processes. This review focuses on the role of SOCE in immunity to infection, allergy, hemostasis and cancer.
authors.affiliation: Department of Biochemistry and Biophysics; McAllister Heart Institute; University of North Carolina; Chapel Hill, NC USA.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bergmeier
authors.affiliation: Department of Pathology; New York University Langone Medical Center; New York, NY USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Weidinger
authors.affiliation: Department of Pathology; New York University Langone Medical Center; New York, NY USA.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Zee
authors.affiliation: Department of Pathology; New York University Langone Medical Center; New York, NY USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Feske
mesh_terms: D056704:Adaptive Immunity; D001792:Blood Platelets / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D006487:Hemostasis; D006801:Humans; D007113:Immunity, Innate; D007239:Infections / Q000276:immunology; D008565:Membrane Proteins / Q000502:physiology*; D009363:Neoplasm Proteins / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism; D000071740:ORAI1 Protein; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1
keywords: CRAC; Ca2+; ORAI1; STIM1; allergy; autoimmunity; calcium; cancer; hemostasis; immunodeficiency; lymphocytes; platelets; tumor,