Differential regulation of mTORC1 by leucine and glutamine

The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates environmental and intracellular signals to regulate cell growth. Amino acids stimulate mTORC1 activation at the lysosome in a manner thought to be dependent on the Rag small guanosine triphosphatases (GTPases), the Ragulator complex, and the vacuolar H(+)-adenosine triphosphatase (v-ATPase). We report that leucine and glutamine stimulate mTORC1 by Rag GTPase-dependent and -independent mechanisms, respectively. Glutamine promoted mTORC1 translocation to the lysosome in RagA and RagB knockout cells and required the v-ATPase but not the Ragulator. Furthermore, we identified the adenosine diphosphate ribosylation factor-1 GTPase to be…

• UD
  U.S. Department of Defense

  Awards: W81XWH, W81XWH-13, W81XWH-13-1-055
• HF
  Hartwell Foundation
• NI
  National Institutes of Health

  Awards: T32GM007752, W81XWH, T32CA121938, R01CA108941, R01GM051586, K99DK099254
• CI
  Canadian Institutes of Health Research