RagA, but Not RagB, Is Essential for Embryonic Development and Adult Mice
Name
Sabatini_ragA but not.pdf
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2.06 MB
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Author(s)
Kirak, Oktay
Efeyan, Alejo
Schweitzer, Lawrence David
Bilate, Angelina M
Chang, Steven H.
Lamming, Dudley
Sabatini, David
Date Issued
April 2014
Journal
Developmental Cell
Publisher
Elsevier
Citation
Efeyan, Alejo; Schweitzer, Lawrence D.; Bilate, Angelina M.; Chang, Steven; Kirak, Oktay; Lamming, Dudley W. and Sabatini, David M. “RagA, but Not RagB, Is Essential for Embryonic Development and Adult Mice.” Developmental Cell 29, no. 3 (May 2014): 321–329. © 2014 Elsevier Inc
Version
Author's final manuscript
Abstract
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.
MIT Department
Broad Institute of MIT and Harvard
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.devcel.2014.03.017
