| First Author | Bainter W | Year | 2021 |
| Journal | J Clin Invest | Volume | 131 |
| Issue | 3 | PubMed ID | 33529166 |
| Mgi Jnum | J:345528 | Mgi Id | MGI:7595957 |
| Doi | 10.1172/JCI140494 | Citation | Bainter W, et al. (2021) Combined immunodeficiency due to a mutation in the gamma1 subunit of the coat protein I complex. J Clin Invest 131(3) |
| abstractText | The coat protein I (COPI) complex mediates retrograde trafficking from the Golgi to the endoplasmic reticulum (ER). Five siblings with persistent bacterial and viral infections and defective humoral and cellular immunity had a homozygous p.K652E mutation in the gamma1 subunit of COPI (gamma1-COP). The mutation disrupts COPI binding to the KDEL receptor and impairs the retrieval of KDEL-bearing chaperones from the Golgi to the ER. Homozygous Copg1K652E mice had increased ER stress in activated T and B cells, poor antibody responses, and normal numbers of T cells that proliferated normally, but underwent increased apoptosis upon activation. Exposure of the mutants to pet store mice caused weight loss, lymphopenia, and defective T cell proliferation that recapitulated the findings in the patients. The ER stress-relieving agent tauroursodeoxycholic acid corrected the immune defects of the mutants and reversed the phenotype they acquired following exposure to pet store mice. This study establishes the role of gamma1-COP in the ER retrieval of KDEL-bearing chaperones and thereby the importance of ER homeostasis in adaptive immunity. |
