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

Gibhardt CS, Cappello S, Bhardwaj R, Schober R, Kirsch S, Bonilla del Rio Z, Gahbauer S, Bochicchio A, Sumanska M, Ickes C, Stejerean-Todoran I, Mitkovski M, Alansary D, Zhang X, Revazian A, Fahrner M, Lunz V, Frischauf I, Luo T, Ezerina D, Messens J, Belousov VV, Hoth M, Böckmann R, Hediger MA, Schindl R, Bogeski I (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 33

Article Number: 108292

Journal Issue: 3

DOI: 10.1016/j.celrep.2020.108292

Abstract

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.

Authors with CRIS profile

Stefan Gahbauer Professur für Computational Biology Anna Bochicchio Professur für Computational Biology Rainer Böckmann Professur für Computational Biology

Involved external institutions

Johannes Kepler Universität (JKU) Linz AT Austria (AT) Vrije Universiteit Brussel (VUB) BE Belgium (BE) Universitätsklinikum des Saarlandes (UKS) DE Germany (DE) Universitätsklinikum Göttingen DE Germany (DE) Universität Bern CH Switzerland (CH) Max-Planck-Institut für Experimentelle Medizin DE Germany (DE) Medizinische Universität Graz AT Austria (AT)

How to cite

APA:

Gibhardt, C.S., Cappello, S., Bhardwaj, R., Schober, R., Kirsch, S., Bonilla del Rio, Z.,... Bogeski, I. (2020). Oxidative Stress-Induced STIM2 Cysteine Modifications Suppress Store-Operated Calcium Entry. Cell Reports, 33(3). https://dx.doi.org/10.1016/j.celrep.2020.108292

MLA:

Gibhardt, Christine Silvia, et al. "Oxidative Stress-Induced STIM2 Cysteine Modifications Suppress Store-Operated Calcium Entry." Cell Reports 33.3 (2020).

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