Shaw Patrick J, Feske Stefan
Department of Pathology, New York University Langone Medical Center, New York, NY 10016, USA.
Front Biosci (Elite Ed). 2012 Jan 1;4(6):2253-68. doi: 10.2741/e540.
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.
钙信号在先天性和适应性免疫反应期间的许多细胞类型特异性效应功能中发挥关键作用。大多数免疫细胞用于提高细胞内（Ca²⁺）的主要机制是储存-操作性Ca²⁺内流（SOCE），即内质网（ER）Ca²⁺储存的耗竭触发细胞外Ca²⁺的流入。免疫细胞中的SOCE由高度Ca²⁺选择性的Ca²⁺释放激活的Ca²⁺（CRAC）通道介导，该通道由ORAI1、ORAI2和ORAI3基因编码。ORAI蛋白由基质相互作用分子（STIM）1和2激活，STIM1和2作为内质网Ca²⁺储存耗竭的传感器。STIM和ORAI蛋白介导的SOCE对免疫功能的重要性从STIM1和ORAI1基因突变患者的免疫缺陷和自身免疫中可见一斑。这些患者以及对基因靶向小鼠的研究揭示了ORAI/STIM蛋白在几种免疫细胞功能中的重要作用。本综述重点关注在理解SOCE在免疫细胞中的作用方面取得的最新进展，重点是人类患者和转基因小鼠中SOCE缺陷导致的免疫失调。
