T Cell Activation Depends on Extracellular Alanine.

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ID: 46884
2019
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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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ronharel2019tcell Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Ron-Harel, Noga;Ghergurovich, Jonathan M;Notarangelo, Giulia;LaFleur, Martin W;Tsubosaka, Yoshiki;Sharpe, Arlene H;Rabinowitz, Joshua D;Haigis, Marcia C;
Journal Cell reports
Year 2019
DOI
S2211-1247(19)31074-5
URL
Keywords
t cells metabolism protein synthesis t cell activation alanine

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