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Publication : Macropinocytosis drives T cell growth by sustaining the activation of mTORC1.

First Author  Charpentier JC Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  180
PubMed ID  31924779 Mgi Jnum  J:283736
Mgi Id  MGI:6388063 Doi  10.1038/s41467-019-13997-3
Citation  Charpentier JC, et al. (2020) Macropinocytosis drives T cell growth by sustaining the activation of mTORC1. Nat Commun 11(1):180
abstractText  Macropinocytosis is an evolutionarily-conserved, large-scale, fluid-phase form of endocytosis that has been ascribed different functions including antigen presentation in macrophages and dendritic cells, regulation of receptor density in neurons, and regulation of tumor growth under nutrient-limiting conditions. However, whether macropinocytosis regulates the expansion of non-transformed mammalian cells is unknown. Here we show that primary mouse and human T cells engage in macropinocytosis that increases in magnitude upon T cell activation to support T cell growth even under amino acid (AA) replete conditions. Mechanistically, macropinocytosis in T cells provides access of extracellular AA to an endolysosomal compartment to sustain activation of the mechanistic target of rapamycin complex 1 (mTORC1) that promotes T cell growth. Our results thus implicate a function of macropinocytosis in mammalian cell growth beyond Ras-transformed tumor cells via sustained mTORC1 activation.
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