{"title":"CRAC通道的生理功能。","authors":"Scott M Emrich, Ryan E Yoast, Mohamed Trebak","doi":"10.1146/annurev-physiol-052521-013426","DOIUrl":null,"url":null,"abstract":"<p><p>Store-operated Ca<sup>2+</sup> entry (SOCE) is a ubiquitous Ca<sup>2+</sup> signaling pathway that is evolutionarily conserved across eukaryotes. SOCE is triggered physiologically when the endoplasmic reticulum (ER) Ca<sup>2+</sup> stores are emptied through activation of inositol 1,4,5-trisphosphate receptors. SOCE is mediated by the Ca<sup>2+</sup> release-activated Ca<sup>2+</sup> (CRAC) channels, which are highly Ca<sup>2+</sup> selective. Upon store depletion, the ER Ca<sup>2+</sup>-sensing STIM proteins aggregate and gain extended conformations spanning the ER-plasma membrane junctional space to bind and activate Orai, the pore-forming proteins of hexameric CRAC channels. In recent years, studies on STIM and Orai tissue-specific knockout mice and gain- and loss-of-function mutations in humans have shed light on the physiological functions of SOCE in various tissues. Here, we describe recent findings on the composition of native CRAC channels and their physiological functions in immune, muscle, secretory, and neuronal systems to draw lessons from transgenic mice and human diseases caused by altered CRAC channel activity.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":null,"pages":null},"PeriodicalIF":15.7000,"publicationDate":"2022-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"37","resultStr":"{\"title\":\"Physiological Functions of CRAC Channels.\",\"authors\":\"Scott M Emrich, Ryan E Yoast, Mohamed Trebak\",\"doi\":\"10.1146/annurev-physiol-052521-013426\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Store-operated Ca<sup>2+</sup> entry (SOCE) is a ubiquitous Ca<sup>2+</sup> signaling pathway that is evolutionarily conserved across eukaryotes. SOCE is triggered physiologically when the endoplasmic reticulum (ER) Ca<sup>2+</sup> stores are emptied through activation of inositol 1,4,5-trisphosphate receptors. SOCE is mediated by the Ca<sup>2+</sup> release-activated Ca<sup>2+</sup> (CRAC) channels, which are highly Ca<sup>2+</sup> selective. Upon store depletion, the ER Ca<sup>2+</sup>-sensing STIM proteins aggregate and gain extended conformations spanning the ER-plasma membrane junctional space to bind and activate Orai, the pore-forming proteins of hexameric CRAC channels. In recent years, studies on STIM and Orai tissue-specific knockout mice and gain- and loss-of-function mutations in humans have shed light on the physiological functions of SOCE in various tissues. Here, we describe recent findings on the composition of native CRAC channels and their physiological functions in immune, muscle, secretory, and neuronal systems to draw lessons from transgenic mice and human diseases caused by altered CRAC channel activity.</p>\",\"PeriodicalId\":8196,\"journal\":{\"name\":\"Annual review of physiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":15.7000,\"publicationDate\":\"2022-02-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"37\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annual review of physiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1146/annurev-physiol-052521-013426\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2021/10/12 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"PHYSIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of physiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1146/annurev-physiol-052521-013426","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/10/12 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
Store-operated Ca2+ entry (SOCE) is a ubiquitous Ca2+ signaling pathway that is evolutionarily conserved across eukaryotes. SOCE is triggered physiologically when the endoplasmic reticulum (ER) Ca2+ stores are emptied through activation of inositol 1,4,5-trisphosphate receptors. SOCE is mediated by the Ca2+ release-activated Ca2+ (CRAC) channels, which are highly Ca2+ selective. Upon store depletion, the ER Ca2+-sensing STIM proteins aggregate and gain extended conformations spanning the ER-plasma membrane junctional space to bind and activate Orai, the pore-forming proteins of hexameric CRAC channels. In recent years, studies on STIM and Orai tissue-specific knockout mice and gain- and loss-of-function mutations in humans have shed light on the physiological functions of SOCE in various tissues. Here, we describe recent findings on the composition of native CRAC channels and their physiological functions in immune, muscle, secretory, and neuronal systems to draw lessons from transgenic mice and human diseases caused by altered CRAC channel activity.
期刊介绍:
Since 1939, the Annual Review of Physiology has been highlighting significant developments in animal physiology. The journal covers diverse areas, including cardiovascular physiology, cell physiology, ecological, evolutionary, and comparative physiology, endocrinology, gastrointestinal physiology, neurophysiology, renal and electrolyte physiology, respiratory physiology, and special topics.