TMEM41B is an endoplasmic reticulum Ca²⁺ release channel maintaining naive T cell quiescence and responsiveness.

ABSTRACT: In mammalian cells, endoplasmic reticulum (ER) passively releases Ca²⁺ 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 Ca²⁺ release channel. Biochemically, purified recombinant TMEM41B forms a concentration-dependent Ca²⁺ channel in single-channel electrophysiology assays. Cellularly, TMEM41B deficiency causes ER Ca²⁺ overload, while overexpression of TMEM41B depletes ER Ca²⁺. Immunologically, ER Ca²⁺ 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 dysregulatio

SUBMITTER: Ma Y 

PROVIDER: S-EPMC11880246 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature