@article{3649,
  keywords = {Animals, Mice, T-Lymphocytes, Alanine, Lymphocyte Activation, Immunologic Memory},
  author = {Noga Ron-Harel and Jonathan Ghergurovich and Giulia Notarangelo and Martin LaFleur and Yoshiki Tsubosaka and Arlene Sharpe and Joshua Rabinowitz and Marcia Haigis},
  title = {T Cell Activation Depends on Extracellular Alanine.},
  abstract = { <p>T cell stimulation is metabolically demanding. To exit quiescence, T~cells rely on environmental nutrients, including glucose and the amino acids glutamine, leucine, serine, and arginine. The expression of transporters for these nutrients is tightly regulated and required for T~cell activation. In contrast to these amino acids, which are essential or require multi-step biosynthesis, alanine can be made from pyruvate by a single transamination. Here, we show that extracellular alanine is nevertheless required for efficient exit from quiescence during naive T~cell activation and memory T~cell restimulation. Alanine deprivation leads to metabolic and functional impairments. Mechanistically, this vulnerability reflects the low expression of alanine aminotransferase, the enzyme required for interconverting pyruvate and alanine, whereas activated T~cells instead induce alanine transporters. Stable isotope tracing reveals that alanine is not catabolized but instead supports protein synthesis. Thus, T~cells depend on exogenous alanine for protein synthesis and normal activation.</p> },
  year = {2019},
  journal = {Cell Rep},
  volume = {28},
  pages = {3011-3021.e4},
  month = {2019 Sep 17},
  issn = {2211-1247},
  doi = {10.1016/j.celrep.2019.08.034},
  language = {eng},
}