Robert A. Saxton
Solved, as a Sabatini-lab graduate student, the structures of the leucine sensor Sestrin2 and the arginine sensor CASTOR1, showing how each one grips its amino acid. He also co-wrote a widely cited 2017 review of mTOR signalling with David Sabatini
Assistant Professor of Immunology and Molecular Medicine and of Chemistry, UC Berkeley (Molecular & Cell Biology) · postdoc, Stanford University (K. Christopher Garcia lab) · PhD, Sabatini lab, Whitehead Institute/MIT
Saxton Lab, UC Berkeley (Berkeley, California, USA) ↗ Lab lineagetrained under David M. Sabatini → ORCID0000-0001-9777-8270 ↗
As a graduate student in David Sabatini's lab, Robert Saxton took on the structural side of a question the lab had just opened: if Sestrin2 and CASTOR1 are the cell's leucine and arginine sensors, what do they actually look like, and how do they grab their amino acid?
Saxton solved the crystal structure of Sestrin2 bound to leucine, showing a single pocket that specifically fits leucine's hydrophobic side chain, and did the equivalent structural work for CASTOR1 and arginine. Together with colleagues in the lab he also helped identify SAMTOR, the sensor for S-adenosylmethionine, rounding out the set of direct amino-acid and metabolite sensors upstream of mTORC1.
The timeline below follows his structural studies gathered in this Atlas.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2014 | M | The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1 CHA2014 Sestrins bind GATOR2 to negatively regulate amino-acid signalling upstream of mTORC1. |
| 2015 | M | Sestrin2 is a leucine sensor for the mTORC1 pathway WOL2015 Sestrin2 is a direct leucine sensor whose leucine binding releases GATOR2 to activate mTORC1. |
| 2015 | M | Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway SAX2015 Solves the crystal structure of Sestrin2 bound to leucine, explaining how a single pocket confers specificity for this one amino acid. |
| 2016 | M | Mechanism of arginine sensing by CASTOR1 upstream of mTORC1 SAX2016 Solves the structural basis for arginine sensing by CASTOR1, the second direct amino-acid sensor upstream of mTORC1. |
| 2016 | M | The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway CHA2016 Identified CASTOR1 as the direct arginine sensor: when arginine binds CASTOR1, it lets go of GATOR2, switching mTORC1 on. Together with Sestrin2 (leucine) this built the picture of mTORC1 as a cell that literally tastes individual amino acids. |
| 2017 | R | mTOR Signaling in Growth, Metabolism, and Disease SAX2017 Comprehensive synthesis of mTORC1/mTORC2 signaling, growth regulation, metabolism, and disease relevance. |
| 2017 | M | SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway GU2017 Helps identify SAMTOR as the direct sensor for S-adenosylmethionine upstream of mTORC1. |
| 2022 | M | Structure of the nutrient-sensing hub GATOR2 VAL2022 Cryo-EM structure of human GATOR2: a 1.1 MDa, two-fold symmetric cage built on an octagonal scaffold decorated with eight pairs of WD40 beta-propellers, and a map of where Sestrin2 and CASTOR1 dock. It substantially advances the GATOR2 side of the sensor module, though how GATOR2 inhibits GATOR1 is still not fully settled. |
Co-authors in the Atlas 22
People with a profile here who share at least one study with Robert A. Saxton.
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- David M. Sabatini 8 shared studies Identified mTOR (as RAFT1) in 1994. His lab then mapped much of the machinery around it: raptor and rictor at the core of mTORC1 and mTORC2, the Rag–Ragulator system that docks mTORC1 on the lysosome, and the sensors that detect leucine, arginine and SAM
- Lynne Chantranupong 6 shared studies Showed as a Sabatini-lab graduate student that the Sestrins act through GATOR2 to regulate amino-acid signalling to mTORC1. She then discovered the CASTOR proteins, the cell's arginine sensors for the pathway
- Sonia M. Scaria 4 shared studies Contributed, as an MIT undergraduate in the Sabatini lab, to the discovery of CASTOR1 as the arginine sensor and SAMTOR as the SAM sensor of the mTORC1 pathway
- Rachel L. Wolfson 3 shared studies Identified Sestrin2 as the direct leucine sensor of the mTORC1 pathway as a Sabatini-lab MD-PhD student. She also co-discovered KICSTOR, the complex that recruits GATOR1 to the lysosome
- Steven P. Gygi 3 shared studies Mass-spectrometry scientist whose Harvard lab builds large-scale proteomics methods, including the BioPlex human protein-interaction map, and contributed proteomics to the discoveries of the CASTOR and SAMTOR nutrient sensors
- J. Wade Harper 2 shared studies Co-discovered the F-box motif that links substrates to SCF ubiquitin ligases, and co-leads with Steven Gygi the BioPlex protein-interaction map, which contributed to the discoveries of the CASTOR and SAMTOR nutrient sensors
- Jose M. Orozco 2 shared studies Researcher trained in David Sabatini's laboratory at the Whitehead Institute and MIT who showed that mTORC1 senses glucose through the glycolysis metabolite DHAP
- Kevin E. Knockenhauer 2 shared studies Structural biologist trained in Thomas Schwartz's MIT lab who helped solve the amino acid sensor structures of Sestrin2 and CASTOR1, and who later moved to drug discovery at Accent Therapeutics
- Kuang Shen 2 shared studies Solved, as a Sabatini-lab postdoc, cryo-EM structures of GATOR1 and of the FLCN–FNIP2–Rag–Ragulator complex, two switches that set mTORC1 activity. His UMass Chan lab studies the structural basis of nutrient sensing
- Thomas U. Schwartz 2 shared studies MIT structural biologist who studies how molecules pass across the nuclear envelope, and whose crystallography lab helped solve the leucine and arginine sensor structures upstream of mTORC1
- Tim Wang 2 shared studies Co-developed genome-wide CRISPR screening in human cells (reported in parallel by Feng Zhang's lab) as a graduate student with David Sabatini and Eric Lander, and contributed to studies showing that the 4E-BPs mediate mTORC1's control of translation and that CASTOR1 senses arginine
- Xin Gu 2 shared studies Cell biologist who discovered SAMTOR, the sensor that lets mTORC1 read the methyl donor SAM, as a PhD student at MIT, and who now leads a lab at Dana-Farber and Harvard Medical School studying ubiquitin-independent protein destruction by the midnolin-proteasome pathway
- Edward J. Brignole Research scientist who directs the cryo-electron microscopy facility at MIT.nano and whose cryo-EM work helped solve the structures of GATOR1, GATOR2 and Raptor docked on the Rag GTPases for the Sabatini lab
- Eric Spooner Manager of the Whitehead Institute's Proteomics Core Facility, whose mass spectrometry work identified proteins in complexes for many Whitehead studies, including two on amino acid sensing upstream of mTORC1
- Grace Y. Liu Wrote with David Sabatini a major 2020 review of mTOR in nutrition, growth and ageing, and in the Sabatini lab studied how mTORC1 senses nutrients such as serine
- Gregory A. Wyant Showed that the lysosomal protein SLC38A9 exports leucine and other essential amino acids out of the lysosome, letting cells grow on proteins they have taken up and broken down there
- Kacper B. Rogala Solved the near-atomic cryo-EM structure that shows how mTORC1 physically docks at the lysosome by reading the Rag GTPases
- Kendall J. Condon Ran genome-wide CRISPR screens revealing how mitochondrial stress signals to mTORC1
- Liron Bar-Peled Showed as a Sabatini-lab graduate student that Ragulator switches the Rag GTPases on, acting as their GEF. He also discovered GATOR1 and GATOR2; GATOR1 switches the Rags off and its genes are mutated in some cancers
- Max L. Valenstein First author of the cryo-EM structures of GATOR2, the hub that tells mTORC1 whether amino acids are present, alone and bound to the sensors Sestrin2 and CASTOR1
- Michael E. Pacold Radiation oncologist and chemical biologist at NYU Langone who studies the metabolism of brain tumours, and a co-author of the Sabatini lab's structure of the leucine sensor Sestrin2
- Pranav V. Lalgudi Co-author of the cryo-EM structures of GATOR2, the nutrient-sensing hub of mTORC1, in 2022 and of GATOR2 bound to Sestrin2 and CASTOR1 in 2025
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