|Title||T Cell Activation Depends on Extracellular Alanine.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Ron-Harel, N, Ghergurovich, JM, Notarangelo, G, LaFleur, MW, Tsubosaka, Y, Sharpe, AH, Rabinowitz, JD, Haigis, MC|
|Date Published||2019 Sep 17|
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.
|Alternate Journal||Cell Rep|