Journal
SCIENCE
Volume 347, Issue 6218, Pages 194-198Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1259472
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Funding
- NIH [R01GM051586, R01CA108941, T32CA121938, T32GM007752, K99DK099254]
- Department of Defense [W81XWH-13-1-055]
- Hartwell Foundation
- Canadian Institutes of Health Research
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The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates environmental and intracellular signals to regulate cell growth. Amino acids stimulatem TORC1 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 required for mTORC1 activation and lysosomal localization by glutamine. Our results uncover a signaling cascade to mTORC1 activation independent of the Rag GTPases and suggest that mTORC1 is differentially regulated by specific amino acids.
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