| First Author | Carreras-Sureda A | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 12 | Pages | 113540 |
| PubMed ID | 38060449 | Mgi Jnum | J:360104 |
| Mgi Id | MGI:7574052 | Doi | 10.1016/j.celrep.2023.113540 |
| Citation | Carreras-Sureda A, et al. (2023) The ER stress sensor IRE1 interacts with STIM1 to promote store-operated calcium entry, T cell activation, and muscular differentiation. Cell Rep 42(12):113540 |
| abstractText | Store-operated Ca(2+) 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 Ca(2+) within the ER lumen during Ca(2+) signaling. Disruption of ER Ca(2+) 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 Ca(2+) 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 Ca(2+) 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. |
