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.
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Dallas, TX 75390-9041, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Wauson
authors.forename: Elma
authors.initials: E
authors.lastname: Zaganjor
authors.forename: A-Young
authors.initials: AY
authors.lastname: Lee
authors.forename: Marcy L
authors.initials: ML
authors.lastname: Guerra
authors.forename: Anwesha B
authors.initials: AB
authors.lastname: Ghosh
authors.forename: Angie L
authors.initials: AL
authors.lastname: Bookout
authors.forename: Chris P
authors.initials: CP
authors.lastname: Chambers
authors.forename: Arif
authors.initials: A
authors.lastname: Jivan
authors.forename: Kathleen
authors.initials: K
authors.lastname: McGlynn
authors.forename: Michele R
authors.initials: MR
authors.lastname: Hutchison
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Deberardinis
authors.forename: Melanie H
authors.initials: MH
authors.lastname: Cobb
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
chemical_list: D000596:Amino Acids; D007328:Insulin; D046912:Multiprotein Complexes; D011506:Proteins; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; C431926:taste receptors, type 1; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases