| First Author | Ma Y | Year | 2025 |
| Journal | Cell Discov | Volume | 11 |
| Issue | 1 | Pages | 18 |
| PubMed ID | 40038246 | Mgi Jnum | J:374297 |
| Mgi Id | MGI:8259516 | Doi | 10.1038/s41421-024-00766-w |
| Citation | Ma Y, et al. (2025) TMEM41B is an endoplasmic reticulum Ca(2+) release channel maintaining naive T cell quiescence and responsiveness. Cell Discov 11(1):18 |
| abstractText | In mammalian cells, endoplasmic reticulum (ER) passively releases Ca(2+) under steady state, but channels involved remain elusive. Here, we report that TMEM41B, an ER-resident membrane protein critical for autophagy, lipid metabolism, and viral infection, functions as an ER Ca(2+) release channel. Biochemically, purified recombinant TMEM41B forms a concentration-dependent Ca(2+) channel in single-channel electrophysiology assays. Cellularly, TMEM41B deficiency causes ER Ca(2+) overload, while overexpression of TMEM41B depletes ER Ca(2+). Immunologically, ER Ca(2+) overload leads to upregulation of IL-2 and IL-7 receptors in naive T cells, which in turn increases basal signaling of JAK-STAT, AKT-mTOR, and MAPK pathways. This dysregulation drives TMEM41B-deficient naive T cells into a metabolically activated yet immunologically naive state. ER Ca(2+) overload also downregulates CD5, lowering the activation threshold of TMEM41B-deficient T cells and leading to heightened T cell responses during infections. In summary, we identify TMEM41B as a concentration-dependent ER Ca(2+) release channel, revealing an unexpected role of ER Ca(2+) in naive T cell quiescence and responsiveness. |
