2. Academic Validation
  3. VMP1 prevents Ca2+ overload in endoplasmic reticulum and maintains naive T cell survival

VMP1 prevents Ca2+ overload in endoplasmic reticulum and maintains naive T cell survival

  • J Exp Med. 2023 Jun 5;220(6):e20221068. doi: 10.1084/jem.20221068.
Ying Liu # 1 2,  Yuying Ma # 1 2,  Jing Xu # 1 2,  Guangyue Zhang # 1 2 3,  Xiaocui Zhao # 1 2 3,  Zihao He 1 2,  Lixia Wang 1 2 3,  Na Yin 1 2,  Min Peng 1 2 3 4
Affiliations

Affiliations

  • 1 Department of Basic Medical Sciences, School of Medicine, Tsinghua University , Beijing, China.
  • 2 Institute for Immunology, Tsinghua University , Beijing, China.
  • 3 Tsinghua-Peking Center for Life Sciences , Beijing, China.
  • 4 Beijing Key Laboratory for Immunological Research on Chronic Diseases, Tsinghua University , Beijing, China.
  • # Contributed equally.
PMID: 36971758 DOI: 10.1084/jem.20221068
Abstract

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.

Figures
Products