The G Protein-Coupled Taste Receptor T1R1/T1R3 Regulates mTORC1 and Autophagy

Eric M. Wauson, Elma Zaganjor, A. Young Lee, Marcy L. Guerra, Anwesha B. Ghosh, Angie L. Bookout, Chris P. Chambers, Arif Jivan, Kathleen McGlynn, Michele R. Hutchison, Ralph J. Deberardinis, Melanie H. Cobb

Research output: Contribution to journalArticle

97 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)851-862
Number of pages12
JournalMolecular Cell
Volume47
Issue number6
DOIs
Publication statusPublished - Sep 28 2012

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Wauson, E. M., Zaganjor, E., Lee, A. Y., Guerra, M. L., Ghosh, A. B., Bookout, A. L., ... Cobb, M. H. (2012). The G Protein-Coupled Taste Receptor T1R1/T1R3 Regulates mTORC1 and Autophagy. Molecular Cell, 47(6), 851-862. https://doi.org/10.1016/j.molcel.2012.08.001