The ER stress sensor IRE1 interacts with STIM1 to promote store-operated calcium entry, T cell activation, and muscular differentiation

Amado Carreras-Sureda; Xin Zhang; Loann Laubry; Jessica Brunetti; Stéphane Koenig; Xiaoxia Wang; Cyril Castelbou; Claudio Hetz; Yong Liu; Maud Frieden; Nicolas Demaurex

Cell Reports (Dec 2023)

The ER stress sensor IRE1 interacts with STIM1 to promote store-operated calcium entry, T cell activation, and muscular differentiation

Amado Carreras-Sureda,
Xin Zhang,
Loann Laubry,
Jessica Brunetti,
Stéphane Koenig,
Xiaoxia Wang,
Cyril Castelbou,
Claudio Hetz,
Yong Liu,
Maud Frieden,
Nicolas Demaurex

Affiliations

Amado Carreras-Sureda: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland; Corresponding author
Xin Zhang: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland
Loann Laubry: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland
Jessica Brunetti: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland
Stéphane Koenig: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland
Xiaoxia Wang: Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Cyril Castelbou: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland
Claudio Hetz: Biomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; FONDAP Center for Geroscience (GERO), Brain Health and Metabolism, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile
Yong Liu: Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, the Institute for Advanced Studies, Wuhan University, Wuhan 430072, China
Maud Frieden: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland
Nicolas Demaurex: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland

Journal volume & issue: Vol. 42, no. 12
p. 113540

Abstract

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Summary: Store-operated Ca2+ entry (SOCE) mediated by stromal interacting molecule (STIM)-gated ORAI channels at endoplasmic reticulum (ER) and plasma membrane (PM) contact sites maintains adequate levels of Ca2+ within the ER lumen during Ca2+ signaling. Disruption of ER Ca2+ homeostasis activates the unfolded protein response (UPR) to restore proteostasis. Here, we report that the UPR transducer inositol-requiring enzyme 1 (IRE1) interacts with STIM1, promotes ER-PM contact sites, and enhances SOCE. IRE1 deficiency reduces T cell activation and human myoblast differentiation. In turn, STIM1 deficiency reduces IRE1 signaling after store depletion. Using a CaMPARI2-based Ca2+ genome-wide screen, we identify CAMKG2 and slc105a as SOCE enhancers during ER stress. Our findings unveil a direct crosstalk between SOCE and UPR via IRE1, acting as key regulator of ER Ca2+ and proteostasis in T cells and muscles. Under ER stress, this IRE1-STIM1 axis boosts SOCE to preserve immune cell functions, a pathway that could be targeted for cancer immunotherapy.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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