Human Diversity in a Cell Surface Receptor that Inhibits Autophagy

Anu Chaudhary, Mara Leite, Bridget R. Kulasekara, Melissa A. Altura, Cassandra Ogahara, Eli Weiss, Wenqing Fu, Marie Pierre Blanc, Michael O'Keeffe, Cox Terhorst, Joshua M. Akey, Samuel I. Miller

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Mutations in genes encoding autophagy proteins have been associated with human autoimmune diseases, suggesting that diversity in autophagy responses could be associated with disease susceptibility or severity. A cellular genome-wide association study (GWAS) screen was performed to explore normal human diversity in responses to rapamycin, a microbial product that induces autophagy. Cells from several human populations demonstrated variability in expression of a cell surface receptor, CD244 (SlamF4, 2B4), that correlated with changes in rapamycin-induced autophagy. High expression of CD244 and receptor activation with its endogenous ligand CD48 inhibited starvation- and rapamycin-induced autophagy by promoting association of CD244 with the autophagy complex proteins Vps34 and Beclin-1. The association of CD244 with this complex reduced Vps34 lipid kinase activity. Lack of CD244 is associated with auto-antibody production in mice, and lower expression of human CD244 has previously been implicated in severity of human rheumatoid arthritis and systemic lupus erythematosus, indicating that increased autophagy as a result of low levels of CD244 may alter disease outcomes.

Original languageEnglish (US)
Pages (from-to)1791-1801
Number of pages11
JournalCurrent Biology
Volume26
Issue number14
DOIs
StatePublished - Jul 25 2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Chaudhary, A., Leite, M., Kulasekara, B. R., Altura, M. A., Ogahara, C., Weiss, E., Fu, W., Blanc, M. P., O'Keeffe, M., Terhorst, C., Akey, J. M., & Miller, S. I. (2016). Human Diversity in a Cell Surface Receptor that Inhibits Autophagy. Current Biology, 26(14), 1791-1801. https://doi.org/10.1016/j.cub.2016.05.003