Document Detail


The G protein-coupled taste receptor T1R1/T1R3 regulates mTORC1 and autophagy.
MedLine Citation:
PMID:  22959271     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
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
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-09-06
Journal Detail:
Title:  Molecular cell     Volume:  47     ISSN:  1097-4164     ISO Abbreviation:  Mol. Cell     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-10-01     Completed Date:  2012-12-20     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  9802571     Medline TA:  Mol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  851-62     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Dallas, TX 75390-9041, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Amino Acids / metabolism
Animals
Autophagy*
Down-Regulation
Extracellular Signal-Regulated MAP Kinases / metabolism
Insulin / metabolism
Insulin-Secreting Cells / metabolism*
Mice
Mice, Knockout
Protein Biosynthesis
Proteins / metabolism*
RNA Interference
RNA, Small Interfering
Receptors, G-Protein-Coupled / genetics*,  metabolism*
Signal Transduction
Grant Support
ID/Acronym/Agency:
5-T32 GM007062/GM/NIGMS NIH HHS; P30 CA142543/CA/NCI NIH HHS; R01 CA157996/CA/NCI NIH HHS; R01 CA157996/CA/NCI NIH HHS; R01 DK055310/DK/NIDDK NIH HHS; R01 DK55310/DK/NIDDK NIH HHS; R37 DK034128/DK/NIDDK NIH HHS; R37 DK34128/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Insulin; 0/Proteins; 0/RNA, Small Interfering; 0/Receptors, G-Protein-Coupled; 0/mechanistic target of rapamycin complex 1; 0/taste receptors, type 1; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Genome-wide screen identifies pathways that govern GAA/TTC repeat fragility and expansions in dividi...
Next Document:  Hepatic expression of HCV RNA-dependent RNA polymerase triggers innate immune signaling and cytokine...