The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway
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Sabatini_The CASTOR.pdf
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Author(s)
Gygi, Melanie P.
Shen, Kuang
Harper, J. Wade
Gygi, Steven P.
Chantranupong, Lynne
Scaria, Sonia M.
Saxton, Robert Andrew
Wyant, Gregory Andrew
Wang, Tim
Sabatini, David
Date Issued
March 2016
Journal
Cell
Publisher
Elsevier
Citation
Chantranupong, Lynne; Scaria, Sonia M.; Saxton, Robert A.; Gygi, Melanie P.; Shen, Kuang; Wyant, Gregory A.; Wang, Tim; Harper, J. Wade; Gygi, Steven P. and Sabatini, David M. “The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway.” Cell 165, no. 1 (March 2016): 153–164. © 2016 Elsevier Inc
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Author's final manuscript
Abstract
Amino acids signal to the mTOR complex I (mTORC1) growth pathway through the Rag GTPases. Multiple distinct complexes regulate the Rags, including GATOR1, a GTPase activating protein (GAP), and GATOR2, a positive regulator of unknown molecular function. Arginine stimulation of cells activates mTORC1, but how it is sensed is not well understood. Recently, SLC38A9 was identified as a putative lysosomal arginine sensor required for arginine to activate mTORC1 but how arginine deprivation represses mTORC1 is unknown. Here, we show that CASTOR1, a previously uncharacterized protein, interacts with GATOR2 and is required for arginine deprivation to inhibit mTORC1. CASTOR1 homodimerizes and can also heterodimerize with the related protein, CASTOR2. Arginine disrupts the CASTOR1-GATOR2 complex by binding to CASTOR1 with a dissociation constant of ∼30 μM, and its arginine-binding capacity is required for arginine to activate mTORC1 in cells. Collectively, these results establish CASTOR1 as an arginine sensor for the mTORC1 pathway.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.cell.2016.02.035
