Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8+ T cell differentiation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-06

AUTHORS

Kristen N Pollizzi, Im-Hong Sun, Chirag H Patel, Ying-Chun Lo, Min-Hee Oh, Adam T Waickman, Ada J Tam, Richard L Blosser, Jiayu Wen, Greg M Delgoffe, Jonathan D Powell

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. More... »

PAGES

704-711

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ni.3438

DOI

http://dx.doi.org/10.1038/ni.3438

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1031118490

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27064374


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