title: Exploring the unique features of the ARC channel, a store-independent Orai channel.
abstract: The discovery of the Orai proteins, and the identification of STIM1 as the molecule that regulates them, was based on their role in the agonist-activated store-operated entry of calcium via the CRAC channels. However, these same proteins are also essential components of the ARC channels responsible for a similar agonist-activated, but store-independent, arachidonic acid-regulated entry of calcium. The fact that these 2 biophysically similar calcium entry pathways frequently co-exist in the same cells suggests that they must each possess different features that allow them to function in distinct ways to regulate specific cellular activities. This review begins to address this question by describing recent findings characterizing the unique features of the ARC channels--their molecular composition, STIM1-dependent activation, and physiological activities--and the importance of defining such features for the accurate therapeutic targeting of these 2 Orai channel subtypes.
authors.affiliation: Department of Pharmacology and Physiology; University of Rochester Medical Center; Rochester, NY USA.
authors.forename: Jill L
authors.initials: JL
authors.lastname: Thompson
authors.affiliation: Department of Pharmacology and Physiology; University of Rochester Medical Center; Rochester, NY USA.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Shuttleworth
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D000071740:ORAI1 Protein; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D016718:Arachidonic Acid; D002118:Calcium
keywords: Orai1; Orai3; arachidonic acid; calcium channel; calcium entry; stromal interacting molecule
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