title: Molecular regulation of the pore component of CRAC channels, Orai1.
abstract: Store-operated Ca(2+) entry (SOCE) is a fundamental mechanism ubiquitously employed by cells to elevate intracellular Ca(2+) concentrations ([Ca(2+)]i). Increased intracellular Ca(2+) ions act as a second messenger that can stimulate a variety of downstream signaling pathways affecting proliferation, secretion, differentiation, and death of cells. In immune cells, immune receptor stimulation induces endoplasmic reticulum Ca(2+) store depletion that subsequently activates Ca(2+)-release-activated-Ca(2+) (CRAC) channels, a prototype of store-operated Ca(2+) (SOC) channels. Identification of Orai1 as the pore subunit of CRAC channels has provided the much-needed molecular tool to dissect the mechanism of activation and regulation of these channels. In this review, we discuss the recent advances in understanding the regulatory mechanisms and posttranslational modifications that regulate diverse aspects of CRAC channel function.
authors.affiliation: Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors.forename: Sonal
authors.initials: S
authors.lastname: Srikanth
authors.forename: Yousang
authors.initials: Y
authors.lastname: Gwack
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating; D008928:Mitochondria / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism; D000071740:ORAI1 Protein; D011499:Protein Processing, Post-Translational; D021381:Protein Transport
chemical_list: C551025:CRACR2A protein, human; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D002147:Calmodulin; C499048:MBP protein, human; D004676:Myelin Basic Protein; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D000262:Adenylyl Cyclases
keywords: CRAC channels; Ca(2+) signaling; Channel gating; Channel inactivation; Orai1; Posttranslational modification; Protein interaction; STIM1