ORAI1 and STIM1 deficiency in human and mice: roles of store-operated Ca2+ entry in the immune system and beyond.
ORAI1 and STIM1 deficiency in human and mice: roles of store-operated Ca2+ entry in the immune system and beyond.
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DOI：
10.1111/j.1600-065x.2009.00818.x
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发表时间：
2009-09
影响因子：
8.7
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中科院分区：
文献类型：
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存储操作的钙内流(SOCE)是包括淋巴细胞和其他免疫细胞在内的许多细胞类型用来增加细胞内钙离子浓度的一种机制，以启动信号转导。免疫受体如T细胞受体、B细胞受体或Fc受体的激活导致内质网(ER)钙库中的钙离子释放，进而激活质膜钙通道，如已知的钙释放激活的钙通道(CRAC)。已鉴定出两个与SOCE有关的基因：ORAI1作为质膜CRAC通道的造孔亚单位，以及基质相互作用分子-1(STIM1)，它们负责感知内质网钙离子浓度并激活ORAI1-CRAC通道。在过去的几年里，人们致力于了解SOCE的分子机制及其在体外和体内对细胞功能的作用。已经建立了许多转基因小鼠模型来研究ORAI1和STIM1在免疫中的作用。此外，在免疫缺陷患者中发现的ORAI1和STIM1突变为了解基因和SOCE的作用提供了有价值的见解。本文综述了ORAI1和STIM1在体内的作用，讨论了ORAI1和STIM1缺陷的人类患者和小鼠的表型。
Store-operated Ca2+ entry (SOCE) is a mechanism used by many cells types including lymphocytes and other immune cells to increase intracellular Ca2+ concentrations to initiate signal transduction. Activation of immunoreceptors such as the T-cell receptor, B-cell receptor, or Fc receptors results in the release of Ca2+ ions from endoplasmic reticulum (ER) Ca2+ stores and subsequent activation of plasma membrane Ca2+ channels such as the well-characterized Ca2+ release-activated Ca2+ (CRAC) channel. Two genes have been identified that are essential for SOCE: ORAI1 as the pore-forming subunit of the CRAC channel in the plasma membrane and stromal interaction molecule-1 (STIM1) sensing the ER Ca2+ concentration and activating ORAI1-CRAC channels. Intense efforts in the past several years have focused on understanding the molecular mechanism of SOCE and the role it plays for cell functions in vitro and in vivo. A number of transgenic mouse models have been generated to investigate the role of ORAI1 and STIM1 in immunity. In addition, mutations in ORAI1 and STIM1 identified in immunodeficient patients provide valuable insight into the role of both genes and SOCE. This review focuses on the role of ORAI1 and STIM1 in vivo, discussing the phenotypes of ORAI1- and STIM1-deficient human patients and mice.