Differential regulation of mTORC1 by leucine and glutamine

Jenna L. Jewell, Young Chul Kim, Ryan C. Russell, Fa Xing Yu, Hyun Woo Park, Steven W. Plouffe, Vincent S. Tagliabracci, Kun Liang Guan

Research output: Contribution to journalArticle

293 Scopus citations

Abstract

Themechanistic 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 lysosomein 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 RagGTPases and suggest that mTORC1 is differentially regulated by specific amino acids.

Original languageEnglish (US)
Pages (from-to)194-198
Number of pages5
JournalScience
Volume347
Issue number6218
DOIs
StatePublished - Jan 9 2015

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    Jewell, J. L., Kim, Y. C., Russell, R. C., Yu, F. X., Park, H. W., Plouffe, S. W., Tagliabracci, V. S., & Guan, K. L. (2015). Differential regulation of mTORC1 by leucine and glutamine. Science, 347(6218), 194-198. https://doi.org/10.1126/science.1259472