Human receptors for sweet and umami taste

Abstract

The three members of the T1R class of taste-specific G proteincoupled receptors have been hypothesized to function in combination as heterodimeric sweet taste receptors. Here we show that human T1R2͞T1R3 recognizes diverse natural and synthetic sweeteners. In contrast, human T1R1͞T1R3 responds to the umami taste stimulus L-glutamate, and this response is enhanced by 5-ribonucleotides, a hallmark of umami taste. The ligand specificities of rat T1R2͞T1R3 and T1R1͞T1R3 correspond to those of their human counterparts. These findings implicate the T1Rs in umami taste and suggest that sweet and umami taste receptors share a common subunit. Large-scale sequencing of a subtracted cDNA library derived from rat taste tissue identified a new C-family G proteincoupled receptor, T1R1, that is expressed selectively in taste receptor cells; T1R1-based degenerate PCR led to the identification of a related taste-specific receptor, T1R2 (1). Recently, a third and possibly final member of the T1R family, T1R3, was identified in the human DNA databank (2-7). Tellingly, mouse T1R3 maps to a genomic interval containing Sac, a locus that influences sweet taste in the mouse (8, 9). Recent highresolution genetic mapping and complementation studies have strengthened the connection between mouse T1R3 and Sac (2-7). Although T1R1 and T1R2 appear to be expressed in predominantly nonoverlapping regions of the tongue, they each are coexpressed with T1R3 (1, 3, 4, 6). These overlapping expression patterns and precedent from the structurally related heterodimeric ␥-aminobutyric acid type B receptor (10-13) suggested that T1R1 and T1R2 may combine with T1R3 to form heterodimeric sweet taste receptors. Indeed, rat T1R2 has been shown recently to function in combination with T1R3 to recognize a subset of sweet taste stimuli, a finding that has been proposed to reflect the involvement of additional combinations of T1Rs in sweet taste (6). In this study we cloned and functionally expressed human and rat T1Rs. Human and rat T1R2͞ T1R3 recognized all sweet taste stimuli tested, and human and rat T1R1͞T1R3 recognized umami taste stimuli. These findings suggest that different combinations of T1Rs function as heterodimeric sweet and umami taste receptors.Material and Methods T1R Cloning. Intronless human T1R expression constructs were generated in a pEAK10-derived vector (Edge Biosystems, Gaithersburg, MD) by a combination of cDNA-based and genomic DNA-based methods. To generate the full-length T1R1 expression construct, two 5Ј coding exons identified in a cloned T1R1 interval (GenBank accession no. AL159177) were combined by PCR overlap and then joined to a 5Ј-truncated testis cDNA clone. The T1R2 expression construct was generated from a partially sequenced T1R2 genomic interval. Two missing T1R2 5Ј introns were identified by screening shotgun libraries of the cloned genomic interval using probes derived from the corresponding rat coding sequence. Coding exons then were combined by PCR overlap to produce the full-length expression construct. The T1R3 e...

Consensus meeting: monosodium glutamate – an update

“…This approach has led to the identification of a set of G-protein-coupled receptors, organized into two receptor families (taste receptor 1 (T1R) and taste receptor 2 (T2R)) that elaborate the basic taste modalities, including umami (Hoon et al, 1999;Nelson et al, 2002;Zhao et al, 2003). Umami taste receptors fall into the T1R family of receptors, and recent studies in knockout mice suggest that a particular member of the T1R family (the T1R1 þ 3 variant) serves as an L-amino-acid receptor in rat taste buds (Zhao et al, 2003), and an umami-specific taste receptor in humans (Li et al, 2002).…”

Food preferences and aversions in human health and nutrition: how can pigs help the biomedical research?

“…Intestinal taste receptor subunits (T1R2 1 T1R3, associated with the gustatory G-protein (gustducin) involved in sweet taste recognition characterized in pigs (Moran et al, 2010b) humans (Li et al, 2002) and rats (Mace et al, 2007) …”

“…Sucram, a combination of saccharin and neohesperidin dihydrochalcone) led to an enhancement of the expression of SGLT1 and of the subsequent intestinal glucose transport function by acting on the intestinal and lingual sweet taste receptor T1R21T1R3, subunits that are associated with the gustatory G-protein gustducin (for a review, see Shirazi-Beechey et al, 2011). These intestinal taste receptor subunits and their involvement in sweet taste recognition have been characterized in pigs (Moran et al, 2010b), humans (Li et al, 2002) and rats (Mace et al, 2007;Sclafani, 2007). Food intake also induces the release of several gut hormones from the endocrine cells of the small and large intestines, such as glucagon-like peptide 1 (GLP-1) or 2 (GLP-2) or the leptin, a hormone that is particularly expressed in adipocytes and acts as a satiety signal.…”

Binding of glutamate to the umami receptor

“…The umami taste receptor is a Class C G protein coupled receptor (GPCR [1]). In humans, it responds to L-glutamate and, to some extent, L-aspartate; in other species, it serves as a more general detector of L-amino acids in the diet [2].…”