| First Author | Ron-Harel N | Year | 2019 |
| Journal | Cell Rep | Volume | 28 |
| Issue | 12 | Pages | 3011-3021.e4 |
| PubMed ID | 31533027 | Mgi Jnum | J:300848 |
| Mgi Id | MGI:6489101 | Doi | 10.1016/j.celrep.2019.08.034 |
| Citation | Ron-Harel N, et al. (2019) T Cell Activation Depends on Extracellular Alanine. Cell Rep 28(12):3011-3021.e4 |
| abstractText | 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. |
