Department of Molecular Chicago, IL 60611 Pharmacology and Biological Chemistry, Northwestern University, Feinberg School of Medicine.
Front Biosci (Landmark Ed). 2012 Jan 1;17(5):1613-26. doi: 10.2741/4007.
Ca2+ is a ubiquitous signaling messenger mediating many essential cellular functions such as excitability, exocytosis and transcription. Among the different pathways by which cellular Ca2+ signals are generated, the entry of Ca2+ through store-operated Ca2+ release-activated Ca2+ (CRAC) channels has emerged as a widespread mechanism for regulating Ca2+ signaling in many eukaryotic cells. CRAC channels are implicated in the physiology and pathophysiology of numerous cell types, underlie several disease processes including a severe combined immunodeficiency syndrome, and have emerged as major targets for drug development. Although little was known of the molecular mechanisms of CRAC channels for several decades, the discovery of Orai1 as a prototypic CRAC channel pore-subunit, and the identification of STIM1 as the ER Ca2+ sensor, have led to rapid progress in our understanding of many aspects of CRAC channel behavior. This review examines the molecular features of the STIM and Orai proteins that regulate the activation and conduction mechanisms of CRAC channels.
钙离子是一种普遍存在的信号信使，介导许多重要的细胞功能，如兴奋性、胞吐和转录。在细胞钙离子信号产生的不同途径中，通过储存操作的钙离子释放激活的钙离子（CRAC）通道进入钙离子已经成为调节许多真核细胞钙离子信号的广泛机制。CRAC 通道与许多细胞类型的生理学和病理生理学有关，是包括严重联合免疫缺陷综合征在内的几种疾病过程的基础，并已成为药物开发的主要靶点。尽管几十年来对 CRAC 通道的分子机制知之甚少，但 Orai1 作为典型的 CRAC 通道孔亚基的发现，以及 STIM1 作为内质网钙离子传感器的鉴定，使得我们对 CRAC 通道行为的许多方面的理解取得了快速进展。这篇综述检查了调节 CRAC 通道激活和传导机制的 STIM 和 Orai 蛋白的分子特征。
