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Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8(+) T cell differentiation.


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-mediate

SUBMITTER: Pollizzi KN 

PROVIDER: S-EPMC4873361 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature