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Scientific article
Open access
English

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

Published inCell reports, vol. 42, no. 12, 113540
Publication date2023-12-26
First online date2023-12-05
Abstract

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.

eng
Keywords
  • 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
Citation (ISO format)
CARRERAS SUREDA, Amado et al. The ER stress sensor IRE1 interacts with STIM1 to promote store-operated calcium entry, T cell activation, and muscular differentiation. In: Cell reports, 2023, vol. 42, n° 12, p. 113540. doi: 10.1016/j.celrep.2023.113540
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Identifiers
ISSN of the journal2211-1247
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