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SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway
Xin Gu1,2,3,4, Jose M Orozco1,2,3,4, Robert A Saxton1,2,3,4
1Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Science (New York, N.Y.)
|November 11, 2017
Summary
SAMTOR, a novel protein, acts as a sensor for S-adenosylmethionine (SAM), linking methionine metabolism to mTORC1 signaling. It inhibits mTORC1 when SAM levels are low, promoting cell growth regulation.
Area of Science:
- Cellular Biology
- Metabolism
- Signal Transduction
Background:
- mTOR complex 1 (mTORC1) is a key regulator of cell growth and metabolism.
- Nutrient availability influences mTORC1 activity through Rag GTPases and lysosomal localization.
- Understanding upstream regulators of mTORC1 is crucial for deciphering cellular responses to environmental cues.
Purpose of the Study:
- To identify and characterize novel regulators of mTORC1 signaling.
- To elucidate the mechanism by which methionine metabolism influences mTORC1 activity.
- To investigate the role of the SAMTOR protein in nutrient sensing.
Main Methods:
- Protein-protein interaction studies to identify SAMTOR's binding partners.
- Biochemical assays to determine the binding kinetics of SAMTOR and S-adenosylmethionine (SAM).
- Cellular experiments to assess mTORC1 signaling in response to methionine availability and SAMTOR manipulation.
Main Results:
- SAMTOR was identified as an inhibitor of mTORC1 signaling by interacting with GATOR1, a Rag GTPase activating protein.
- S-adenosylmethionine (SAM) directly binds to SAMTOR, disrupting the SAMTOR-GATOR1 complex.
- Methionine starvation reduces cellular SAM levels, promoting SAMTOR-GATOR1 association and inhibiting mTORC1 signaling in a SAMTOR-dependent manner.
Conclusions:
- SAMTOR functions as a sensor for SAM, directly linking methionine and one-carbon metabolism to mTORC1 signaling.
- The SAM binding capacity of SAMTOR is essential for methionine-induced mTORC1 activation.
- SAMTOR represents a novel molecular link between metabolic status and the regulation of cell growth.
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