| First Author | Liu Y | Year | 2023 |
| Journal | J Exp Med | Volume | 220 |
| Issue | 6 | PubMed ID | 36971758 |
| Mgi Jnum | J:357749 | Mgi Id | MGI:7532507 |
| Doi | 10.1084/jem.20221068 | Citation | Liu Y, et al. (2023) VMP1 prevents Ca2+ overload in endoplasmic reticulum and maintains naive T cell survival. J Exp Med 220(6) |
| abstractText | Ca2+ in endoplasmic reticulum (ER) dictates T cell activation, proliferation, and function via store-operated Ca2+ entry. How naive T cells maintain an appropriate level of Ca2+ in ER remains poorly understood. Here, we show that the ER transmembrane protein VMP1 is essential for maintaining ER Ca2+ homeostasis in naive T cells. VMP1 promotes Ca2+ release from ER under steady state, and its deficiency leads to ER Ca2+ overload, ER stress, and secondary Ca2+ overload in mitochondria, resulting in massive apoptosis of naive T cells and defective T cell response. Aspartic acid 272 (D272) of VMP1 is critical for its ER Ca2+ releasing activity, and a knockin mouse strain with D272 mutated to asparagine (D272N) demonstrates all functions of VMP1 in T cells in vivo depend on its regulation of ER Ca2+. These data uncover an indispensable role of VMP1 in preventing ER Ca2+ overload and maintaining naive T cell survival. |
