SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway
Author(s)
Harper, J. Wade; Gygi, Steven P.; Gu, Xin; Orozco Segrera, Jose; Saxton, Robert Andrew; Condon, Kendall Janine; Liu, Grace Yun; Krawczyk, Patrycja A.; Scaria, Sonia M.; Sabatini, David; ... Show more Show less
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mTOR complex 1 (mTORC1) regulates cell growth and metabolism in response to multiple environmental cues. Nutrients signal via the Rag guanosine triphosphatases (GTPases) to promote the localization of mTORC1 to the lysosomal surface, its site of activation. We identified SAMTOR, a previously uncharacterized protein, which inhibits mTORC1 signaling by interacting with GATOR1, the GTPase activating protein (GAP) for RagA/B. We found that the methyl donor S-adenosylmethionine (SAM) disrupts the SAMTOR-GATOR1 complex by binding directly to SAMTOR with a dissociation constant of approximately 7 μM. In cells, methionine starvation reduces SAM levels below this dissociation constant and promotes the association of SAMTOR with GATOR1, thereby inhibiting mTORC1 signaling in a SAMTOR-dependent fashion. Methionine-induced activation of mTORC1 requires the SAM binding capacity of SAMTOR. Thus, SAMTOR is a SAM sensor that links methionine and one-carbon metabolism to mTORC1 signaling.
Date issued
2017-11Department
Massachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research; Koch Institute for Integrative Cancer Research at MITJournal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Gu, Xin et al. “SAMTOR Is anS-Adenosylmethionine Sensor for the mTORC1 Pathway.” Science 358, no. 6364 (November 9, 2017): 813–818.
Version: Author's final manuscript
ISSN
0036-8075
1095-9203