Oliver's mTOR Atlas Evidence Platform
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Lynne Chantranupong

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

Assistant Professor of Biology, Boston University (since 2024) · postdoc and Hanna Gray Fellow, Harvard Medical School (Bernardo Sabatini lab, 2016–2023) · PhD in Biology, MIT (David Sabatini lab, 2016) · BSc, University of Texas at Austin (2010)

Chantranupong Lab, Boston University (Boston, Massachusetts, USA) ↗ Lab lineagetrained under David M. Sabatini →

Lynne Chantranupong Portrait: Boston University Dept. of Biology

As a graduate student in David Sabatini's lab, Lynne Chantranupong helped identify GATOR1 and GATOR2, two multi-protein complexes that act as an off-switch and on-switch, respectively, for amino-acid signalling to mTORC1. She then showed that the Sestrin proteins bind directly to GATOR2, providing the missing physical link between intracellular leucine levels and this signalling machine.

That work, alongside the CASTOR1 arginine-sensor discovery, completed a core piece of the amino-acid-sensing pathway upstream of mTORC1: sensor proteins that directly bind specific amino acids and relay that information through GATOR1/2 and the Rag GTPases. Chantranupong later did postdoctoral work in neuroscience and now leads her own lab at Boston University.

The timeline below follows her contributions gathered in this Atlas.

Milestones in the Atlas

A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.

YearEvidenceStudy
2012 M A unifying model for mTORC1-mediated regulation of mRNA translation THO2012 Used ribosome profiling with the complete inhibitor Torin1 to address a long-standing debate: in these cells, mTORC1's translational control runs largely through the 4E-BP family acting on a specific class of mRNAs (TOP motifs). Losing just the 4E-BPs makes translation of TOP mRNAs resistant to mTOR inhibition - naming them the master effectors.
2013 M The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1 TSU2013 FLCN-FNIP is a GAP for RagC/D; GDP-bound RagC/D is required for the Rag heterodimer to bind mTORC1, promoting its lysosomal recruitment and activation by amino acids.
2013 M A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1 BAR2013 Co-discovers GATOR1, a tumor-suppressor complex with GAP activity that switches off Rag-GTPase signalling to mTORC1 in the absence of amino acids.
2014 M The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1 CHA2014 Shows the Sestrins bind GATOR2 to negatively regulate the amino-acid-sensing pathway 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, revealing the molecular pocket that lets it act as mTORC1's dedicated leucine sensor.
2015 M Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1 WAN2015 The lysosomal transporter SLC38A9 signals arginine sufficiency to mTORC1.
2016 M Mechanism of arginine sensing by CASTOR1 upstream of mTORC1 SAX2016 CASTOR1 is a direct arginine sensor upstream of mTORC1; structure reveals the arginine-binding mechanism.
2016 M The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway CHA2016 Co-identifies the CASTOR proteins as direct arginine sensors for the mTORC1 pathway.
2017 M KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1 WOL2017 KICSTOR tethers GATOR1 to the lysosome, required for nutrient control of mTORC1.
2018 M Architecture of the human GATOR1 and GATOR1-Rag GTPases complexes SHE2018 Cryo-EM structures of GATOR1 and GATOR1-Rag complexes reveal GAP and inhibitory-clamp mechanisms.
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 33

People with a profile here who share at least one study with Lynne Chantranupong.

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  • David M. Sabatini 12 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
  • Robert A. Saxton 6 shared studies 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
  • Kuang Shen 5 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
  • Rachel L. Wolfson 5 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
  • Tim Wang 5 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
  • Liron Bar-Peled 4 shared studies 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
  • 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
  • Gregory A. Wyant 3 shared studies 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
  • Edward J. Brignole 2 shared studies 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 2 shared studies 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
  • Choah Kim 2 shared studies Researcher in David Sabatini's lab at the Whitehead Institute who contributed to three studies on how amino acids at the lysosome are sensed by mTORC1
  • 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
  • Kendall J. Condon 2 shared studies Ran genome-wide CRISPR screens revealing how mitochondrial stress signals to mTORC1
  • 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
  • Max L. Valenstein 2 shared studies 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
  • Roberto Zoncu 2 shared studies Showed as a postdoc that mTORC1 senses amino acids from inside the lysosome, through the v-ATPase and Ragulator. His Berkeley lab has since mapped how the Rag GTPases and the folliculin complex switch mTORC1 on, and how lysosomal cholesterol feeds into the same system
  • Steven P. Gygi 2 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
  • 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
  • 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
  • Zhi-Yang Tsun 2 shared studies Biologist who, as first author in David Sabatini's lab, showed that the tumour suppressor folliculin is a GAP for the RagC and RagD GTPases that carry the amino acid signal to mTORC1
  • Brian C. Grabiner Catalogued cancer-associated MTOR mutations and showed that many of them hyperactivate the kinase and can predict sensitivity to rapamycin; he also contributed to the discovery of GATOR1
  • Carson C. Thoreen Used Torin1, one of the first ATP-competitive mTOR inhibitors, to reveal functions of mTORC1 that rapamycin cannot block. He then showed that mTORC1 controls translation of mRNAs for the protein-making machinery mainly through the 4E-BP proteins
  • Elizabeth D. Yuan Second author on the study showing that S6K1 phosphorylates BMAL1 to link mTOR signalling with circadian protein synthesis, and co-author on the follow-up in tuberous sclerosis models.
  • J. Wade Harper 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
  • Kacper B. Rogala Solved the near-atomic cryo-EM structure that shows how mTORC1 physically docks at the lysosome by reading the Rag GTPases
  • Kathleen Ottina Researcher in David Sabatini's lab at the Whitehead Institute and HHMI at MIT who contributed to studies of the GATOR1 amino acid off-switch, mTORC1 feedback on growth-factor signalling, and cancer drug resistance
  • Matthew Meyerson Cancer geneticist whose group has helped identify key genes mutated in lung cancer, and who contributed the cancer-genome analysis to the discovery that GATOR1 is a tumour suppressor acting on mTORC1
  • 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
  • Monther Abu-Remaileh Worked out how to isolate lysosomes fast enough to measure what is inside them, and found that mTOR controls what gets out
  • Nathanael S. Gray Medicinal chemist whose lab designed Torin1, an ATP-competitive mTOR inhibitor that blocks functions of mTORC1 that rapamycin misses. His lab is also known for covalent kinase inhibitors and targeted protein degraders
  • 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
  • Rick K. Huang Cryo-electron microscopy specialist who, at the HHMI Janelia Research Campus, helped solve the 2018 and 2019 structures of the protein machines that pass amino acid signals to mTORC1
  • Shuyu Wang Co-discovered SLC38A9 as a Sabatini-lab MD-PhD student, a lysosomal amino-acid transporter that signals arginine sufficiency to mTORC1

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