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.

Genetic Variation in Taste and Its Influence on Food Selection

“…Alpha-gustducin, which is a G-protein coupled receptor subunit, is proposed to be one pathway involved in transmitting the signal downstream once the sweet taste receptor is activated by its ligand (Margolskee, 2002;Sainz et al, 2007). Bitter and umami taste receptors could also transmit their signal via alpha-gustducin (Margolskee, 2002;Sainz et al, 2007). Thus, in addition to understanding taste receptors, understanding the downstream transduction pathway is key to obtaining a complete picture of taste perception.…”

“…It was later discovered that T1R3 in combination with T1R1 is the heteromer responsible for umami taste detection (Nelson et al, 2002). Alpha-gustducin, which is a G-protein coupled receptor subunit, is proposed to be one pathway involved in transmitting the signal downstream once the sweet taste receptor is activated by its ligand (Margolskee, 2002;Sainz et al, 2007). Bitter and umami taste receptors could also transmit their signal via alpha-gustducin (Margolskee, 2002;Sainz et al, 2007).…”

Ric-8A, a Gα protein guanine nucleotide exchange factor potentiates taste receptor signaling

“…Several studies have investigated the importance of G-proteins in taste transduction or the coupling of Tas1Rs and Tas2Rs to G-proteins. The report that knock-out mice for Gα-gustducin have diminished but not abolished sensitivity to sweet and bitter compounds (Wong et al, 1996) which can be rescued by Gα-transducin expression together with heterologous expression studies showing that Gαgus is able to couple to the Tas1Rs and Tas2Rs are consistent with an important role of this G-protein in taste signal transduction (Li et al, 2002; Ueda et al, 2003; Sainz et al, 2007b). Here we report for the first time that Gαgus and Gαt2 physically interact with Ric-8A a GDP/GTP exchange factor expressed in type II taste cells.…”

“…Note that some IP3R-3 positive cells have also been reported to express markers specific for type III cells such as SNAP-25 a synaptic protein found in mouse taste buds (DeFazio et al, 2006); since we report that 100% of IP3R-3 positive cells are also positive for Ric-8A its function in these cell types may be linked to GPCRs present in these cells. Gαgus and Gαi have been shown to couple to Tas1Rs (Li et al, 2002; Ozeck et al, 2004; Sainz et al, 2007b) and Gαt1 to play a role in behavioral and electrophysiological taste responses to umami (He et al, 2004); it is therefore plausible that Ric-8A might amplify the signaling of these receptors as well.…”

Moleküle und biologische Mechanismen des Süß‐ und Umamigeschmacks

“…Süßgeschmack-Untereinheiten ermöglicht wird. [121] Einige Studien haben sich darauf konzentriert, die Frage zu beantworten, welche Einzelnucleotidpolymorphismen (SNPs) in menschlichen T1R1-und T1R3-Genen vorkommen und ob diese SNPs wie beschrieben individuelle Unterschiede bei der Umamiwahrnehmung durch den Menschen hervorrufen können. [122] Die Mehrzahl der nichtsynonymen SNPs wurde im Gen der umamispezifischen Untereinheit T1R1 identifiziert.…”