Physiological and pathophysiological functions of SOCE in the immune system.
Calcium signals play a critical role in many cell-type specific effector functions during innate and adaptive immune responses. The predominant mechanism to raise intracellular (Ca²⁺) used by most immune cells is store-operated Ca²⁺ entry (SOCE), whereby the depletion of endoplasmic reticulum (ER) Ca²⁺ stores triggers the influx of extracellular Ca²⁺. SOCE in immune cells is mediated by the highly Ca²⁺ selective Ca²⁺-release-activated Ca²⁺ (CRAC) channel, encoded by ORAI1, ORAI2 and ORAI3 genes. ORAI proteins are activated by stromal interaction molecules (STIM) 1 and 2, which act as sensors of ER Ca²⁺ store depletion. The importance of SOCE mediated by STIM and ORAI proteins for immune function is evident from the immunodeficiency and autoimmunity in patients with mutations in STIM1 and ORAI1 genes. These patients and studies in gene-targeted mice have revealed an essential role for ORAI/STIM proteins in the function of several immune cells. This review focuses on recent advances made towards understanding the role of SOCE in immune cells with an emphasis on the immune dysregulation that results from defects in SOCE in human patients and transgenic mice.
Department of Pathology, New York University Langone Medical Center, New York, NY 10016, USA.
Patrick J
PJ
Shaw
Stefan
S
Feske
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000473:pathology / Q000503:physiopathology*; D017136:Ion Transport; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology; D000071740:ORAI1 Protein; D000071737:Stromal Interaction Molecule 1
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; D002118:Calcium