title: Redox modulation of STIM-ORAI signaling.
abstract: STIM1 and ORAI1 constitute the core machinery of the ubiquitous store-operated calcium entry pathway and loss of function in these proteins is associated with severe immune and muscular disorders. Other isoforms-STIM1L, STIM2, ORAI2 and ORAI3 exhibit varied expression levels in different cell types along with several other interaction partners and thereby play different roles to facilitate, regulate and fine-tune the calcium entry. STIM proteins convey the Ca(2+) store-depletion message to the PM and thereby participate in refilling of the ER by physically interacting with the Ca(2+)-selective ORAI channels at the PM. STIM and ORAI are exposed to oxidative modifications in the ER, the cytosol, and at the cell surface, and redox-mediated alterations in STIM/ORAI coupling might contribute to autoimmune disorders and cancer progression. This review discusses the redox reactivity of cysteine residues in STIM and ORAI isoforms, focusing on the oxidative modifications of STIM and ORAI proteins by which STIM-ORAI signaling can be modulated.
authors.affiliation: Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse 28, CH-3012 Bern, Switzerland. Electronic address: rajesh.rajesh@ibmm.unibe.ch.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Bhardwaj
authors.affiliation: Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse 28, CH-3012 Bern, Switzerland.
authors.forename: Matthias A
authors.initials: MA
authors.lastname: Hediger
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva, 1 rue Michel-Servet CH-1211 Geneva 4, Switzerland. Electronic address: Nicolas.Demaurex@unige.ch.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Demaurex
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D008954:Models, Biological; D000071740:ORAI1 Protein / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D000071737:Stromal Interaction Molecule 1 / Q000378:metabolism*
chemical_list: D000071740:ORAI1 Protein; D017382:Reactive Oxygen Species; D000071737:Stromal Interaction Molecule 1
keywords: CRAC; Hypoxia; ORAI; ROS; Redox; STIM; Store-operated calcium entry