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

文献类型：期刊论文

作者Ma, Yuying2,3,4; Wang, Yi1,5; Zhao, Xiaocui2,3,4; Jin, Gang2,3,4; Xu, Jing2,3,4; Li, Zhuoyang2,3,4; Yin, Na2,3,4; Gao, Zhaobing1,5; Xia, Bingqing1,5; Peng, Min2,3,4
刊名CELL DISCOVERY
出版日期2025-03-04
卷号11期号:1页码:17
DOI10.1038/s41421-024-00766-w
英文摘要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 dysregulation drives TMEM41B-deficient naive T cells into a metabolically activated yet immunologically naive state. ER Ca2+ 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 Ca2+ release channel, revealing an unexpected role of ER Ca2+ in naive T cell quiescence and responsiveness.
WOS关键词HOMEOSTASIS ; STORES ; LEAK
资助项目National Natural Science Foundation of China (NO.82350108), Tsinghua University DUSHI Program (NO.52302102323), Tsinghua-Peking Center for Life Sciences, SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine, Vanke Special Fund for Public Hea[82350108] ; National Natural Science Foundation of China (NO.82350108), Tsinghua University DUSHI Program (NO.52302102323), Tsinghua-Peking Center for Life Sciences, SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine, Vanke Special Fund for Public Hea[52302102323] ; National Natural Science Foundation of China ; Tsinghua-Peking Center for Life Sciences[2022Z82WKJ013] ; Vanke Special Fund for Public Health and Health Discipline Development Tsinghua University[81825021] ; National Science Fund of Distinguished Young Scholars[22QA1411000] ; Shanghai Rising-Star Program
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:001439315000001
出版者SPRINGERNATURE
源URL[http://119.78.100.183/handle/2S10ELR8/316523]  
专题新药研究国家重点实验室
通讯作者Gao, Zhaobing; Xia, Bingqing; Peng, Min
作者单位1.Univ Chinese Acad Sci, Beijing, Peoples R China
2.Tsinghua Univ, Sch Basic Med Sci, State Key Lab Mol Oncol, Beijing Key Lab Immunol Res Chron Dis,Inst Immunol, Beijing, Peoples R China
3.Shanxi Med Univ, SXMU Tsinghua Collaborat Innovat Ctr Frontier Med, Taiyuan, Shanxi, Peoples R China
4.Tsinghua Peking Ctr Life Sci, Beijing, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, State Key Lab Drug Res, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Ma, Yuying,Wang, Yi,Zhao, Xiaocui,et al. TMEM41B is an endoplasmic reticulum Ca2+ release channel maintaining naive T cell quiescence and responsiveness[J]. CELL DISCOVERY,2025,11(1):17.
APA Ma, Yuying.,Wang, Yi.,Zhao, Xiaocui.,Jin, Gang.,Xu, Jing.,...&Peng, Min.(2025).TMEM41B is an endoplasmic reticulum Ca2+ release channel maintaining naive T cell quiescence and responsiveness.CELL DISCOVERY,11(1),17.
MLA Ma, Yuying,et al."TMEM41B is an endoplasmic reticulum Ca2+ release channel maintaining naive T cell quiescence and responsiveness".CELL DISCOVERY 11.1(2025):17.

入库方式： OAI收割

来源：上海药物研究所

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