Taste receptor type 1 member 3 is a protein that in humans is encoded by the TAS1R3gene.[1][2] The TAS1R3 gene encodes the human homolog of mouse Sac taste receptor, a major determinant of differences between sweet-sensitive and -insensitive mouse strains in their responsiveness to sucrose, saccharin, and other sweeteners.[2][3]
The protein encoded by the TAS1R3 gene is a G protein-coupled receptor with seven trans-membrane domains and is a component of the heterodimeric amino acidtaste receptor TAS1R1+3 and sweettaste receptor TAS1R2+3. This receptor is formed as a protein dimer with either TAS1R1 or TAS1R2.[4]
Experiments have also shown that a homo-dimer of TAS1R3 is also sensitive to natural sugar substances. This has been hypothesized as the mechanism by which sugar substitutes do not have the same taste qualities as natural sugars.[5]
Ligands
The G protein-coupled receptors for sweet and umami taste are formed by dimers of the TAS1R proteins.
The TAS1R1+3 taste receptor is sensitive to the glutamate in MSG as well as the synergistic taste-enhancer molecules inosine monophosphate (IMP) and guanosine monophosphate (GMP). These taste-enhancer molecules are unable to activate the receptor alone, but are rather used to enhance receptor responses many to L-amino acids.[6] The TAS1R2+3 receptor has been shown to respond to natural sugars sucrose and fructose, and to artificial sweeteners saccharin, acesulfame potassium, dulcin, guanidinoacetic acid.[4]
Signal transduction
TAS1R2 and TAS1R1 receptors have been shown to bind to G proteins, most often the gustducin Gα subunit, although a gusducin knock-out has shown small residual activity. TAS1R2 and TAS1R1 have also been shown to activate Gαo and Gαi protein subunits.[7] This suggests that TAS1R1 and TAS1R2 are G protein-coupled receptors that inhibit adenylyl cyclases to decrease cyclic guanosine monophosphate (cGMP) levels in taste receptors.[8] The TAS1R3 protein, however, has been shown in vitro to couple with Gα subunits at a much lower rate than the other TAS1R proteins. While the protein structures of the TAS1R proteins are similar, this experiment shows that the G protein-coupling properties of TAS1R3 may be less important in the transduction of taste signals than the TAS1R1 and TAS1R2 proteins.[7]
Location and innervation
TAS1R1+3 expressing cells are found in fungiform papillae at the tip and edges of the tongue and palate taste receptor cells in the roof of the mouth.[4] These cells are shown to synapse upon the chorda tympani nerves to send their signals to the brain.[6] TAS1R2+3 expressing cells are found in circumvallate papillae and foliate papillae near the back of the tongue and palate taste receptor cells in the roof of the mouth.[4] These cells are shown to synapse upon the glossopharyngeal nerves to send their signals to the brain.[9][10] TAS1R and TAS2R (bitter) channels are not expressed together in any taste buds.[4]
↑ 7.07.1Sainz E, Cavenagh MM, LopezJimenez ND, Gutierrez JC, Battey JF, Northup JK, Sullivan SL (2007). "The G-protein coupling properties of the human sweet and amino acid taste receptors". Developmental Neurobiology. 67 (7): 948–959. doi:10.1002/dneu.20403. PMID17506496.
↑Abaffy T, Trubey KR, Chaudhari N (2003). "Adenylyl cyclase expression and modulation of cAMP in rat taste cells". American Journal of Physiology. Cell Physiology. 284 (6): C1420–C1428. doi:10.1152/ajpcell.00556.2002. PMID12606315.
Max M, Shanker YG, Huang L, Rong M, Liu Z, Campagne F, Weinstein H, Damak S, Margolskee RF (2001). "Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac". Nat. Genet. 28 (1): 58–63. doi:10.1038/88270. PMID11326277.
Spadaccini R, Trabucco F, Saviano G, Picone D, Crescenzi O, Tancredi T, Temussi PA (2003). "The mechanism of interaction of sweet proteins with the T1R2-T1R3 receptor: evidence from the solution structure of G16A-MNEI". J. Mol. Biol. 328 (3): 683–92. doi:10.1016/S0022-2836(03)00346-2. PMID12706725.
Ariyasu T, Matsumoto S, Kyono F, Hanaya T, Arai S, Ikeda M, Kurimoto M (2004). "Taste receptor T1R3 is an essential molecule for the cellular recognition of the disaccharide trehalose". In Vitro Cell. Dev. Biol. Anim. 39 (1–2): 80–8. doi:10.1290/1543-706X(2003)039<0080:TRTIAE>2.0.CO;2. PMID12892531.
Jiang P, Ji Q, Liu Z, Snyder LA, Benard LM, Margolskee RF, Max M (2004). "The cysteine-rich region of T1R3 determines responses to intensely sweet proteins". J. Biol. Chem. 279 (43): 45068–75. doi:10.1074/jbc.M406779200. PMID15299024.
Taniguchi K (2005). "Expression of the sweet receptor protein, T1R3, in the human liver and pancreas". J. Vet. Med. Sci. 66 (11): 1311–4. doi:10.1292/jvms.66.1311. PMID15585941.
Jiang P, Cui M, Zhao B, Liu Z, Snyder LA, Benard LM, Osman R, Margolskee RF, Max M (2005). "Lactisole interacts with the transmembrane domains of human T1R3 to inhibit sweet taste". J. Biol. Chem. 280 (15): 15238–46. doi:10.1074/jbc.M414287200. PMID15668251.
Behrens M, Bartelt J, Reichling C, Winnig M, Kuhn C, Meyerhof W (2006). "Members of RTP and REEP gene families influence functional bitter taste receptor expression". J. Biol. Chem. 281 (29): 20650–9. doi:10.1074/jbc.M513637200. PMID16720576.
Koizumi A, Nakajima K, Asakura T, Morita Y, Ito K, Shmizu-Ibuka A, Misaka T, Abe K (2007). "Taste-modifying sweet protein, neoculin, is received at human T1R3 amino terminal domain". Biochem. Biophys. Res. Commun. 358 (2): 585–9. doi:10.1016/j.bbrc.2007.04.171. PMID17499612.