T Cell Activation Depends on Extracellular Alanine.
Cell Rep
; 28(12): 3011-3021.e4, 2019 09 17.
Article
en En
| MEDLINE
| ID: mdl-31533027
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Activación de Linfocitos
/
Linfocitos T
/
Alanina
/
Memoria Inmunológica
Límite:
Animals
Idioma:
En
Revista:
Cell Rep
Año:
2019
Tipo del documento:
Article