[PDF][PDF] T cell activation depends on extracellular alanine

N Ron-Harel, JM Ghergurovich, G Notarangelo… - Cell reports, 2019 - cell.com
N Ron-Harel, JM Ghergurovich, G Notarangelo, MW LaFleur, Y Tsubosaka, AH Sharpe…
Cell reports, 2019cell.com
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 …
Summary
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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