Metabolism. Differential regulation of mTORC1 by leucine and glutamine
- PMID: 25567907
- PMCID: PMC4384888
- DOI: 10.1126/science.1259472
Metabolism. Differential regulation of mTORC1 by leucine and glutamine
Abstract
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 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.
Copyright © 2015, American Association for the Advancement of Science.
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Comment in
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Cell biology. Making sense of amino acid sensing.Science. 2015 Jan 9;347(6218):128-9. doi: 10.1126/science.aaa4570. Science. 2015. PMID: 25574008 No abstract available.
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