Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8(+) T cell differentiation.
Nat Immunol
; 17(6): 704-11, 2016 06.
Article
em En
| MEDLINE
| ID: mdl-27064374
ABSTRACT
The asymmetric partitioning of fate-determining proteins has been shown to contribute to the generation of CD8(+) effector and memory T cell precursors. Here we demonstrate the asymmetric partitioning of mTORC1 activity after the activation of naive CD8(+) T cells. This results in the generation of two daughter T cells, one of which shows increased mTORC1 activity, increased glycolytic activity and increased expression of effector molecules. The other daughter T cell has relatively low mTORC1 activity and increased lipid metabolism, expresses increased amounts of anti-apoptotic molecules and subsequently displays enhanced long-term survival. Mechanistically, we demonstrate a link between T cell antigen receptor (TCR)-induced asymmetric expression of amino acid transporters and RagC-mediated translocation of mTOR to the lysosomes. Overall, our data provide important insight into how mTORC1-mediated metabolic reprogramming affects the fate decisions of T cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Divisão Celular
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Linfócitos T CD8-Positivos
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Complexos Multiproteicos
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Células Precursoras de Linfócitos T
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Serina-Treonina Quinases TOR
/
Lisossomos
Limite:
Animals
Idioma:
En
Revista:
Nat Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos