@article{ee5f2242ce6f4280a3f2852c448a0e87,
title = "The G Protein-Coupled Taste Receptor T1R1/T1R3 Regulates mTORC1 and Autophagy",
abstract = "Cells continually assess their energy and nutrient state to maintain growth and survival and engage necessary homeostatic mechanisms. Cell-autonomous responses to the fed state require the surveillance of the availability of amino acids and other nutrients. The mammalian target of rapamycin complex 1 (mTORC1) integrates information on nutrient and amino acid availability to support protein synthesis and cell growth. We identify the G protein-coupled receptor (GPCR) T1R1/T1R3 as a direct sensor of the fed state and amino acid availability. Knocking down this receptor, which is found in most tissues, reduces the ability of amino acids to signal to mTORC1. Interfering with this receptor alters localization of mTORC1, downregulates expression of pathway inhibitors, upregulates key amino acid transporters, blocks translation initiation, and induces autophagy. These findings reveal a mechanism for communicating amino acid availability through a GPCR to mTORC1 in mammals.",
author = "Wauson, {Eric M.} and Elma Zaganjor and Lee, {A. Young} and Guerra, {Marcy L.} and Ghosh, {Anwesha B.} and Bookout, {Angie L.} and Chambers, {Chris P.} and Arif Jivan and Kathleen McGlynn and Hutchison, {Michele R.} and Deberardinis, {Ralph J.} and Cobb, {Melanie H.}",
note = "Funding Information: We thank David Mangelsdorf, Steven Kliewer, Joseph Albanesi, Elliott Ross, Gray Pearson (Department of Pharmacology), Michael White (Department of Cell Biology), Ondine Cleaver (Department of Molecular Biology), James Brugarolas (Department of Internal Medicine), and Sylvia Vega-Rubin-de-Celis from the Brugarolas Lab, Natalie Ahn (University of Colorado, Boulder, CO), and members of the M.H.C. lab for comments and suggestions, Nizar Ghneim for early analysis of amino acid starvation, Svetlana Earnest for technical assistance, and Dionne Ware for administrative assistance. The islets and nonendocrine pancreatic tissue were provided by the Islet Resource Facility supported by the University of Alabama, Birmingham, Comprehensive Diabetes Center. This work was supported by grants from the National Institutes of Health (R01 DK55310 and R37 DK34128 to M.H.C. and R01 CA157996 to R.J.D.) and the Robert A. Welch Foundation (I1243 to M.H.C.). During the majority of this work, E.M.W. was supported by a mentor-based postdoctoral fellowship from the American Diabetes Association, A-Y.L. was supported by a training grant from the Cancer Prevention and Research Institute of Texas, and A.L.B. was supported by NIGMS Pharmacological Sciences training Grant 5-T32 GM007062. ",
year = "2012",
month = sep,
day = "28",
doi = "10.1016/j.molcel.2012.08.001",
language = "English (US)",
volume = "47",
pages = "851--862",
journal = "Molecular cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "6",
}