Alternative titles; symbols
HGNC Approved Gene Symbol: TAS1R1
Cytogenetic location: 1p36.31 Genomic coordinates (GRCh38) : 1:6,555,307-6,579,755 (from NCBI)
A heterotrimer of TAS1R1 and TAS1R3 (605865) mediates umami taste perception in mammals. TAS1R1 and TAS1R3 are class C G protein-coupled receptors (summary by Toda et al., 2013).
Bjarnadottir et al. (2005) stated that the deduced 841-amino acid TAS1R1 protein contains the 7 transmembrane domains characteristic of G protein-coupled receptors. They identified TAS1R1 orthologs in mouse and fish. The deduced mouse protein contains 842 amino acids.
Bjarnadottir et al. (2005) determined that the TAS1R1 gene contains 6 exons.
Nelson et al. (2001) mapped the mouse T1r1, T1r2, and T1r3 genes to distal chromosome 4.
By searching the human genome database, Liao and Schultz (2003) found that the T1R1, T1R2, and T1R3 genes are all located within a small region of chromosome 1p36. This region is syntenic to the distal end of mouse chromosome 4, which contains the Sac (saccharin preference) locus that is involved in detecting sweet tastants. Liao and Schultz (2003) found that DVL1 (601365), a genetic marker which is linked to the Sac locus, is within 1,700 bp of T1R3.
Nelson et al. (2001) characterized the mammalian sweet taste receptors T1r1, T1r2 (606226), and T1r3 (605865). Using a heterologous expression system, they demonstrated that mouse T1r2 and T1r3 combine to function as a receptor recognizing sweet-tasting molecules as diverse as sucrose, saccharin, dulcin, and acesulfame-K. Human, rat, and mouse T1Rs are only 70% identical. The authors presented a detailed analysis of the patterns of expression of T1rs and T2rs (bitter taste receptors), thus providing a view of the representation of sweet and bitter taste at the periphery. Nelson et al. (2001) predicted a minimum of 3 and a maximum of 5 sweet receptor genes.
Nelson et al. (2002) identified and characterized a mammalian amino acid taste receptor, T1R1+3, as a heteromer of the T1R1 and T1R3 G protein-coupled receptors. Nelson et al. (2002) demonstrated that T1R1 and T1R3 combine to function as a broadly tuned L-amino acid sensor responding to most of the 20 standard amino acids, but not to their D-enantiomers or other compounds. They also demonstrated that sequence differences in T1R receptors within and between species (human and mouse) can significantly influence the selectivity and specificity of taste responses. Most amino acids that are perceived as sweet (e.g., alanine, glutamine, serine, threonine, or glycine) activate T1R1+3. The responses are strictly dependent on the combined presence of T1R1 and TIR3. T1R1+3 is prominently expressed in fungiform taste buds, which are innervated by chorda tympani fibers. Nelson et al. (2002) generated heteromeric receptors consisting of human and rodent T1R subunits and assayed for activation by amino acids and artificial sweeteners. The presence of human T1R1 or T1R2 greatly altered the sensitivity of the amino acid receptor and the specificity of the sweet receptor. Cells expressing human T1R1 are more than an order of magnitude more sensitive to glutamate than to other amino acids, and cells expressing human T1R2 robustly respond to aspartame, cyclamate, and intensely sweet proteins.
By in situ hybridization, Liao and Schultz (2003) found that all 3 T1R genes are expressed selectively in human taste receptor cells in the fungiform papillae, consistent with their role in taste perception.
Xu et al. (2004) demonstrated the different functional roles of T1R extracellular and transmembrane domains in ligand recognition and G protein coupling. Similar to other G protein-coupled receptors of family C, the N-terminal venus flytrap domain of T1R2 is required for recognizing sweeteners, such as aspartame and neotame. The G protein coupling requires the transmembrane domain of T1R2. Surprisingly, the C-terminal transmembrane domain of T1R3 is required for recognizing sweetener cyclamate and sweet taste inhibitor lactisole. Because T1R3 is the common subunit of the sweet taste receptor and the umami taste receptor, Xu et al. (2004) tested the interaction of lactisole and cyclamate with the umami taste receptor. Lactisole inhibited the activity of the human T1R1/T1R3 receptor and, as predicted, blocked the umami taste of L-glutamate in human taste tests. Cyclamate did not activate the T1R1/T1R3 receptor by itself, but potentiated the receptor's response to L-glutamate. Taken together, these findings demonstrated the different functional roles of T1R3 and T1R2 and the presence of multiple ligand binding sites on the sweet taste receptor.
Chandrashekar et al. (2006) reviewed the receptors and cells for mammalian taste.
Toda et al. (2013) noted that the human T1R1/T1R3 heteromeric complex responds to L-glu, whereas the mouse complex responds more strongly to other L-amino acids. Using human-mouse chimeric receptors and mutation analysis, they identified 12 key residues in the extracellular venus flytrap domain of T1R1 that modulated amino acid recognition. Residues critical for human responses were located at the orthosteric ligand-binding site, whereas the key residues for the broad response of mice were located at regions outside both the orthosteric binding site and the allosteric binding site for inosine-5-prime-monophosphate (IMP), a natural umami taste enhancer. Site-directed mutagenesis studies demonstrated that the key residues for mouse receptor responses modulated receptor activity in a manner distinct from allosteric modulation via IMP. Toda et al. (2013) concluded that changes in the properties of both orthosteric and nonorthosteric sites of T1R1 underlie the determination of ligand specificity in mammalian T1R1/T1R3.
Sweet and umami (the taste of monosodium glutamate) are the main attractive taste modalities in humans. T1Rs are mammalian taste receptors that combine to assemble 2 heteromeric G protein-coupled receptor complexes: T1R1+3, an umami sensor, and T1R2+3, a sweet receptor. Zhao et al. (2003) reported the behavioral and physiologic characterization of T1r1, T1r2, and T1r3 knockout mice. They demonstrated that sweet and umami taste were strictly dependent on T1R receptors and showed that selective elimination of T1R subunits differentially abolished detection and perception of these 2 taste modalities. To examine the basis of sweet tastant recognition and coding, they engineered animals expressing either the human T1R2 receptor or a modified engineered opioid receptor, RASSL, in sweet cells. Expression of T1R2 in mice generated animals with humanized sweet taste preferences, while expression of RASSL drove strong attraction to a synthetic opiate, demonstrating that sweet cells trigger dedicated behavioral outputs, but their tastant selectivity is determined by the nature of the receptors.
Bjarnadottir, T. K., Fredriksson, R., Schioth, H. B. The gene repertoire and the common evolutionary history of glutamate, pheromone (V2R), taste(1) and other related G protein-coupled receptors. Gene 362: 70-84, 2005. [PubMed: 16229975] [Full Text: https://doi.org/10.1016/j.gene.2005.07.029]
Chandrashekar, J., Hoon, M. A., Ryba, N. J. P., Zuker, C. S. The receptors and cells for mammalian taste. Nature 444: 288-294, 2006. [PubMed: 17108952] [Full Text: https://doi.org/10.1038/nature05401]
Liao, J., Schultz, P. G. Three sweet receptor genes are clustered in human chromosome 1. Mammalian Genome 14: 291-301, 2003. [PubMed: 12856281] [Full Text: https://doi.org/10.1007/s00335-002-2233-0]
Nelson, G., Chandrashekar, J., Hoon, M. A., Feng, L., Zhao, G., Ryba, N. J. P., Zuker, C. S. An amino-acid taste receptor. Nature 416: 199-202, 2002. [PubMed: 11894099] [Full Text: https://doi.org/10.1038/nature726]
Nelson, G., Hoon, M. A., Chandrashekar, J., Zhang, Y., Ryba, N. J. P., Zuker, C. S. Mammalian sweet taste receptors. Cell 106: 381-390, 2001. [PubMed: 11509186] [Full Text: https://doi.org/10.1016/s0092-8674(01)00451-2]
Toda, Y., Nakagita, T., Hayakawa, T., Okada, S., Narukawa, M., Imai, H., Ishimaru, Y., Misaka, T. Two distinct determinants of ligand specificity in T1R1/T1R3 (the umami taste receptor). J. Biol. Chem. 288: 36863-36877, 2013. [PubMed: 24214976] [Full Text: https://doi.org/10.1074/jbc.M113.494443]
Xu, H., Staszewski, L., Tang, H., Adler, E., Zoller, M., Li, X. Different functional roles of T1R subunits in the heteromeric taste receptors. Proc. Nat. Acad. Sci. 101: 14258-14263, 2004. [PubMed: 15353592] [Full Text: https://doi.org/10.1073/pnas.0404384101]
Zhao, G. Q., Zhang, Y., Hoon, M. A., Chandrashekar, J., Erlenbach, I., Ryba, N. J. P., Zuker, C. S. The receptors for mammalian sweet and umami taste. Cell 115: 255-266, 2003. [PubMed: 14636554] [Full Text: https://doi.org/10.1016/s0092-8674(03)00844-4]