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

Article Article scientifique Article The ER stress sensor IRE1 interacts with STIM1 to promote store-operated calcium entry, T cell activation, and muscular differentiation eng 2023-12-05 2023-12-26 author Carreras Sureda Amado Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland. Electronic address: amado.carrerassureda@unige.ch. 918518 Département de physiologie cellulaire et métabolisme (PHYME) author Zhang Xin Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland. 875594 author Laubry Loann Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland. 974391 Département de physiologie cellulaire et métabolisme (PHYME) author Brunetti Jessica Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland. 868672 author Konig Stéphane 0000-0002-0801-279X Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland. 133957 Structure enseignement (ENSI) author Wang Xiaoxiao Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China. author Castelbou Cyril Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland. 30263 Département de physiologie cellulaire et métabolisme (PHYME) author Hetz Claudio 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. author Liu Yong Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, the Institute for Advanced Studies, Wuhan University, Wuhan 430072, China. author Frieden Maud 0000-0001-7135-0874 Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland. 45900 Département de physiologie cellulaire et métabolisme (PHYME) author Demaurex Nicolas 0000-0002-9933-6772 Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland. 24642 Département de physiologie cellulaire et métabolisme (PHYME) 113540 10.1016/j.celrep.2023.113540 38060449 2211-1247 https://www.sciencedirect.com/science/article/pii/S2211124723015528 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. CP: Cell biology CP: Immunology CRISPR screening CaMPARI ER stress IRE1 SOCE STIM1 T cells Calcium Muscle Humans Calcium / metabolism Calcium Channels / metabolism Calcium Signaling / physiology Cell Membrane / metabolism Neoplasm Proteins / metabolism ORAI1 Protein / metabolism Protein Serine-Threonine Kinases / metabolism Stromal Interaction Molecule 1 / metabolism Dewey 612 Swiss National Science Foundation Calcium, from human reserve cells to matured myofibers 184756 CH Projects Swiss National Science Foundation Calcium signaling at membrane contact sites during phagocytosis 189042 CH Projects 134 Département de physiologie cellulaire et métabolisme 21C false 168 Signaux intracellulaires 210 1232 Régénération du muscle squelettique 986 https://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD046579 https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-13548?query=e-mtab-13548 https://data.mendeley.com/datasets/4zyx9gbhzt/1 Cell reports 42 12 c3865c46-b24d-4059-9c7b-9b8af745b3f3 Article (Published version) Public 1-s2.0-S2211124723015528-main.pdf 5086928 application/pdf CC BY-NC-ND-4.0 14a575114d156fa97d1ca81d7462db164e54cfd62b1aabfa4a836042df50c64f cac5857c-26ba-41b8-b119-54a50e979bda Supplemental data Public ScienceDirect_files_15May2024_06-45.zip 15384894 application/zip 8c95dac94006754573afefb7d7af0da77eb8380c2cbf6ddd5144b2e33ee592e2 Vignette Public 1-s2.0-S2211124723015528-fx1.jpg 171320 image/png openAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme

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The ER stress sensor IRE1 interacts with STIM1 to promote store-operated calcium entry, T cell activation, and muscular differentiation	Cell reports			2023	241	251

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