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Developmental cell DOI:10.1016/j.devcel.2014.03.017

RagA, but Not RagB, Is Essential for Embryonic Development and Adult Mice.

Publication TypeJournal Article
Year of Publication2014
AuthorsEfeyan, A, Schweitzer, LD, Bilate, AM, Chang, S, Kirak, O, Lamming, DW, Sabatini, DM
JournalDevelopmental cell
Date Published2014/04/22

The mechanistic target of rapamycin complex 1 (mTORC1) integrates cues from growth factors and nutrients to control metabolism. In contrast to the growth factor input, genetic disruption of nutrient-dependent activation of mTORC1 in mammals remains unexplored. We engineered mice lacking RagA and RagB genes, which encode the GTPases responsible for mTORC1 activation by nutrients. RagB has limited expression, and its loss shows no effects on mammalian physiology. RagA deficiency leads to E10.5 embryonic death, loss of mTORC1 activity, and severe growth defects. Primary cells derived from these mice exhibit no regulation of mTORC1 by nutrients and maintain high sensitivity to growth factors. Deletion of RagA in adult mice is lethal. Upon RagA loss, a myeloid population expands in peripheral tissues. RagA-specific deletion in liver increases cellular responses to growth factors. These results show the essentiality of nutrient sensing for mTORC1 activity in mice and its suppression of PI3K/Akt signaling.