T Cell Activation Depends on Extracellular Alanine.

T Cell Activation Depends on Extracellular Alanine.

Ron-Harel, Noga;Ghergurovich, Jonathan M;Notarangelo, Giulia;LaFleur, Martin W;Tsubosaka, Yoshiki;Sharpe, Arlene H;Rabinowitz, Joshua D;Haigis, Marcia C;
Cell reports 2019 Vol. 28 pp. 3011-3021.e4
229
ronharel2019tcell

Abstract

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.

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