Lynne Chantranupong
Identified the Sestrins and GATOR1/2 in the amino-acid-sensing pathway
PhD, University of Texas at Austin · graduate work, Sabatini lab, Whitehead Institute/MIT · Assistant Professor of Biology, Boston University
Chantranupong Lab, Boston University ↗
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
| Year | Evidence | Study |
|---|---|---|
| 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 resistant to mTOR inhibition - naming them the master effectors. |
| 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. |
| 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. |
| 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. |