CRAC channelopathies.
CRAC channelopathies.
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DOI：
10.1007/s00424-009-0777-5
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发表时间：
2010-07
影响因子：
4.5
通讯作者：
Feske, Stefan
中科院分区：
文献类型：
--
作者：
Feske, Stefan
关键词：
储存操作的Ca2+进入（SOCE）是许多非兴奋性和一些兴奋性细胞中重要的Ca2+内流途径。它受细胞内Ca2+储存的填充状态，特别是内质网（ER）的调节。[Ca2+]ER的减少导致质膜Ca2+通道的激活，介导持续的Ca2+内流，这是许多细胞功能以及Ca2+储存的再填充所必需的。Ca2+释放激活Ca2+ (CRAC)通道是表征最好的SOC通道，具有明确的电生理特性。近年来，长期神秘的CRAC通道的分子组成已被确定。ORAI1（或CRACM1）是质膜中CRAC通道的成孔亚基。基质相互作用分子（STIM） 1定位于内质网，感知[Ca2+]内质网，并通过与ORAI1结合激活储存量耗尽的CRAC通道。这两种蛋白在人和小鼠的许多组织中广泛表达，这与SOCE和CRAC通道电流在许多细胞类型中的广泛流行一致。在STIM1和ORAI1突变的人类患者中，CRAC通道病变的特征是CRAC通道电流消失，缺乏SOCE和临床免疫缺陷，先天性肌病和无水外胚层发育不良。本文综述了ORAI和STIM蛋白在多种细胞类型和组织中对SOCE和CRAC通道功能的作用，并比较了ORAI1和stim1缺陷的人患者和靶向缺失ORAI和STIM基因的小鼠的表型。
Store-operated Ca2+ entry (SOCE) is an important Ca2+ influx pathway in many non-excitable and some excitable cells. It is regulated by the filling state of intracellular Ca2+ stores, notably the endoplasmic reticulum (ER). Reduction in [Ca2+]ER results in activation of plasma membrane Ca2+ channels that mediate sustained Ca2+ influx which is required for many cell functions as well as refilling of Ca2+ stores. The Ca2+ release activated Ca2+ (CRAC) channel is the best characterized SOC channel with well-defined electrophysiological properties. In recent years, the molecular components of the CRAC channel, long mysterious, have been defined. ORAI1 (or CRACM1) acts as the pore-forming subunit of the CRAC channel in the plasma membrane. Stromal interaction molecule (STIM) 1 is localized in the ER, senses [Ca2+]ER, and activates the CRAC channel upon store depletion by binding to ORAI1. Both proteins are widely expressed in many tissues in both human and mouse consistent with the widespread prevalence of SOCE and CRAC channel currents in many cells types. CRAC channelopathies in human patients with mutations in STIM1 and ORAI1 are characterized by abolished CRAC channel currents, lack of SOCE and—clinically—immunodeficiency, congenital myopathy, and anhydrotic ectodermal dysplasia. This article reviews the role of ORAI and STIM proteins for SOCE and CRAC channel function in a variety of cell types and tissues and compares the phenotypes of ORAI1 and STIM1-deficient human patients and mice with targeted deletion of Orai and Stim genes.
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DOI：
10.1111/j.1440-1681.2008.05095.x
发表时间：
2009-01-01
影响因子：
2.9
作者：
Barritt, Greg J.;Litjens, Tom L.;Rychkov, Grigori Y.
通讯作者：
Rychkov, Grigori Y.
影响因子：
20.3
作者：
Braun, Attila;Varga-Szabo, David;Nieswandt, Bernhard
通讯作者：
Nieswandt, Bernhard
影响因子：
4.8
作者：
Darbellay, Basile;Arnaudeau, Serge;Bernheim, Laurent
通讯作者：
Bernheim, Laurent
影响因子：
20.3
作者：
Bergmeier, Wolfgang;Oh-hora, Masatsugu;Feske, Stefan
通讯作者：
Feske, Stefan
影响因子：
4
作者：
Alicia, Sampieri;Angelica, Zepeda;Vaca, Luis
通讯作者：
Vaca, Luis