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Redox modulation of STIM-ORAI signaling

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Bhardwaj Rajesh, Hediger Matthias A., Demaurex Nicolas,
Project Store-operated calcium channels in health and disease
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Original article (peer-reviewed)

Journal Cell Calcium
Volume (Issue) 60(2)
Page(s) 142 - 152
Title of proceedings Cell Calcium
DOI 10.1016/j.ceca.2016.03.006

Open Access

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 Ca2+ store-depletion message to the PM and thereby participate in refilling of the ER by physically interacting with the Ca2+-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.
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