title: The G-protein coupling properties of the human sweet and amino acid taste receptors.
abstract: The human T1R taste receptors are family C G-protein-coupled receptors (GPCRs) that act as heterodimers to mediate sweet (hT1R2 + hT1R3) and umami (hT1R1 + hT1R3) taste modalities. Each T1R has a large extracellular ligand-binding domain linked to a seven transmembrane-spanning core domain (7TMD). We demonstrate that the 7TMDs of hT1R1 and hT1R2 display robust ligand-independent constitutive activity, efficiently catalyzing the exchange of GDP for GTP on Galpha subunits. In contrast, relative to the 7TMDs of hT1R1 and hT1R2, the 7TMD of hT1R3 couples poorly to G-proteins, suggesting that in vivo signaling may proceed primarily through hT1R1 and hT1R2. In addition, we provide direct evidence that the hT1Rs selectively signal through Galpha(i/o) pathways, coupling to multiple Galpha(i/o) subunits as well as the taste cell specific Gbeta(1)gamma(13) dimer.
authors.affiliation: Section on G-protein Coupled Receptors, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sainz
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Cavenagh
authors.forename: Nelson D
authors.initials: ND
authors.lastname: LopezJimenez
authors.forename: Joanne C
authors.initials: JC
authors.lastname: Gutierrez
authors.forename: James F
authors.initials: JF
authors.lastname: Battey
authors.forename: John K
authors.initials: JK
authors.lastname: Northup
authors.forename: Susan L
authors.initials: SL
authors.lastname: Sullivan
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D017434:Protein Structure, Tertiary / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013549:Sweetening Agents / Q000378:metabolism; D013649:Taste / Q000502:physiology*; D013650:Taste Buds / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D044385:GTP-Binding Protein alpha Subunits; D044387:GTP-Binding Protein beta Subunits; D043562:Receptors, G-Protein-Coupled; D013549:Sweetening Agents; C431926:taste receptors, type 1; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate