Oxidative Stress-Induced STIM2 Cysteine Modifications Suppress Store-Operated Calcium Entry.

Gibhardt, Christine Silvia; Cappello, Sabrina; Bhardwaj, Rajesh; Schober, Romana; Kirsch, Sonja Agnes; Bonilla Del Rio, Zuriñe; Gahbauer, Stefan; Bochicchio, Anna; Sumanska, Magdalena; Ickes, Christian; Stejerean-Todoran, Ioana; Mitkovski, Miso; Alansary, Dalia; Zhang, Xin; Revazian, Aram; Fahrner, Marc; Lunz, Victoria; Frischauf, Irene; Luo, Ting; Ezerina, Daria; ... (2020). Oxidative Stress-Induced STIM2 Cysteine Modifications Suppress Store-Operated Calcium Entry. Cell reports, 33(3), p. 108292. Cell Press 10.1016/j.celrep.2020.108292

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Store-operated calcium entry (SOCE) through STIM-gated ORAI channels governs vital cellular functions. In this context, SOCE controls cellular redox signaling and is itself regulated by redox modifications. However, the molecular mechanisms underlying this calcium-redox interplay and the functional outcomes are not fully understood. Here, we examine the role of STIM2 in SOCE redox regulation. Redox proteomics identify cysteine 313 as the main redox sensor of STIM2 in vitro and in vivo. Oxidative stress suppresses SOCE and calcium currents in cells overexpressing STIM2 and ORAI1, an effect that is abolished by mutation of cysteine 313. FLIM and FRET microscopy, together with MD simulations, indicate that oxidative modifications of cysteine 313 alter STIM2 activation dynamics and thereby hinder STIM2-mediated gating of ORAI1. In summary, this study establishes STIM2-controlled redox regulation of SOCE as a mechanism that affects several calcium-regulated physiological processes, as well as stress-induced pathologies.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie

UniBE Contributor:

Bhardwaj, Rajesh and Hediger, Matthias

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2211-1247

Publisher:

Cell Press

Language:

English

Submitter:

Verena de Serra Frazao-Bill

Date Deposited:

22 Dec 2020 09:56

Last Modified:

22 Dec 2020 10:06

Publisher DOI:

10.1016/j.celrep.2020.108292

PubMed ID:

33086068

Uncontrolled Keywords:

I(CRAC) ORAI ROS SOCE STIM2 calcium cysteine melanoma redox thiol

BORIS DOI:

10.7892/boris.149494

URI:

https://boris.unibe.ch/id/eprint/149494

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