Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac

Abstract

The ability to taste the sweetness of carbohydrate-rich foodstuffs has a critical role in the nutritional status of humans. Although several components of bitter transduction pathways have been identified, the receptors and other sweet transduction elements remain unknown. The Sac locus in mouse, mapped to the distal end of chromosome 4 (refs. 7-9), is the major determinant of differences between sweet-sensitive and -insensitive strains of mice in their responsiveness to saccharin, sucrose and other sweeteners. To identify the human Sac locus, we searched for candidate genes within a region of approximately one million base pairs of the sequenced human genome syntenous to the region of Sac in mouse. From this search, we identified a likely candidate: T1R3, a previously unknown G protein-coupled receptor (GPCR) and the only GPCR in this region. Mouse Tas1r3 (encoding T1r3) maps to within 20,000 bp of the marker closest to Sac (ref. 9) and, like human TAS1R3, is expressed selectively in taste receptor cells. By comparing the sequence of Tas1r3 from several independently derived strains of mice, we identified a specific polymorphism that assorts between taster and non-taster strains. According to models of its structure, T1r3 from non-tasters is predicted to have an extra amino-terminal glycosylation site that, if used, would interfere with dimerization.

Taste and pheromone perception in the fruit fly Drosophila melanogaster

“…Putative taste receptors were discovered almost simultaneously in Drosophila and mammals. Although all these receptors belong to the large super family of GTP-binding (G) protein-coupled receptors (GPCRs), the fly GRs share no significant sequence similarity with their mammalian counterparts [33][34][35][36][37][38][39][40][41][42]. The fly Gr gene family was discovered by analyzing the Drosophila genome database using algorithms that identify multitransmembrane proteins or by performing reiterated Basic Local Alignment Search Tool searches with Drosophila olfactory receptor proteins as query sequences [35,36,42], and once the entire Drosophila genome sequence was determined, a total of 68 Gr genes were found (Fig.…”

Binding of glutamate to the umami receptor

“…Homology modeling of the closely related sweet taste receptors (T1R2 + T1R3) has facilitated an understanding of the interactions of sweeteners with their receptor [7][8][9][10][11][12].…”

A Drosophila gustatory receptor required for the responses to sucrose, glucose, and maltose identified by mRNA tagging

“…In contrast, the umami response appears to be mediated by a T1R1/T1R3 heteromer (7,(14)(15)(16). Surprisingly, two receptors, T1R2 and T1R3, may account for all responses to sugars through distinct combinations of T1R2/T1R3 heteromers and/or T1R2 and T1R3 homomultimers (7,(14)(15)(16)(17)(18)(19)(20). In Drosophila there is a single family of 68 Grs (21)(22)(23)(24), and the proportion devoted to sweet, as opposed to bitter, tastants is unresolved.…”