Macropinocytosis drives T cell growth by sustaining the activation of mTORC1

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. Macropinocytosis has been implicated in the expansion of transformed cells when nutrient-depleted. Here the authors show that macropinocytosis also contributes to the expansion of primary T cells even under nutrient-replete conditions, potentially by providing access of extracellular amino acids to an endolysosomal compartment to sustain mTORC1 activation.