TAS1R3

Taste receptor type 1 member 3 is a protein that in humans is encoded by the TAS1R3 gene.[5][6] 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.[6][7]

TAS1R3
Identifiers
Aliases	TAS1R3, T1R3, taste 1 receptor member 3
External IDs	OMIM: 605865 MGI: 1933547 HomoloGene: 12890 GeneCards: TAS1R3
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p36.33 Start 1,331,280 bp[1] End 1,335,314 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4 E2|4 87.65 cM Start 155,859,268 bp[2] End 155,863,362 bp[2]
Gene ontology Molecular function • G-protein coupled receptor activity • signal transducer activity • taste receptor activity • protein heterodimerization activity • sweet taste receptor activity • signaling receptor activity Cellular component • integral component of membrane • cell membrane • sweet taste receptor complex • membrane • integral component of plasma membrane Biological process • sensory perception of taste • sensory perception of sweet taste • sensory perception of umami taste • detection of chemical stimulus involved in sensory perception of sweet taste • signal transduction • response to stimulus • G-protein coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	83756	83771
Ensembl	ENSG00000169962	ENSMUSG00000029072
UniProt	Q7RTX0	Q925D8
RefSeq (mRNA)	NM_152228	NM_031872
RefSeq (protein)	NP_689414	NP_114078
Location (UCSC)	Chr 1: 1.33 – 1.34 Mb	Chr 4: 155.86 – 155.86 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Structure

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 acid taste receptor TAS1R1+3 and sweet taste receptor TAS1R2+3. This receptor is formed as a protein dimer with either TAS1R1 or TAS1R2.[8] 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.[9]

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 monosodium glutamate (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.[10] 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.[8]

Signal transduction

TAS1R2 and TAS1R1 receptors have been shown to bind to G proteins, most often the gustducin Gα subunit, although a gustducin knock-out has shown small residual activity. TAS1R2 and TAS1R1 have also been shown to activate Gαo and Gαi protein subunits.[11] 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.[12] 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.[11]

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.[8] These cells are shown to synapse upon the chorda tympani nerves to send their signals to the brain.[10] 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.[8] These cells are shown to synapse upon the glossopharyngeal nerves to send their signals to the brain.[13][14] TAS1R and TAS2R (bitter) channels are not expressed together in any taste buds.[8]

References

1. GRCh38: Ensembl release 89: ENSG00000169962 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000029072 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Montmayeur JP, Liberles SD, Matsunami H, Buck LB (Apr 2001). "A candidate taste receptor gene near a sweet taste locus". Nat Neurosci. 4 (5): 492–8. doi:10.1038/87440. PMID 11319557.
6. "Entrez Gene: TAS1R3 taste receptor, type 1, member 3".
7. Bachmanov, Alexander A.; Li, Xia; Reed, Danielle R.; Ohmen, Jeffery D.; Li, Shanru; Chen, Zhenyu; Tordoff, Michael G.; de Jong, Pieter J.; Wu, Chenyan (2001). "Positional cloning of the mouse saccharin preference (Sac) locus". Chemical Senses. 26 (7): 925–933. doi:10.1093/chemse/26.7.925. ISSN 0379-864X. PMC 3644801. PMID 11555487.
8. Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS (2001). "Mammalian sweet taste receptors". Cell. 106 (3): 381–390. doi:10.1016/S0092-8674(01)00451-2. PMID 11509186.
9. Zhao GQ, Zhang Y, Hoon MA, Chandrashekar J, Erlenbach I, Ryba NJ, Zuker CS (2003). "The receptors for mammalian sweet and umami taste". Cell. 115 (3): 255–266. doi:10.1016/S0092-8674(03)00844-4. PMID 14636554.
10. Nelson G, Chandrashekar J, Hoon MA, Feng L, Zhao G, Ryba NJ, Zuker CS (2002). "An amino-acid taste receptor". Nature. 416 (6877): 199–202. Bibcode:2002Natur.416..199N. doi:10.1038/nature726. PMID 11894099.
11. Sainz 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. PMID 17506496.
12. 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. PMID 12606315.
13. Beamis JF, Shapshay SM, Setzer S, Dumon JF (1989). "Teaching models for Nd:YAG laser bronchoscopy". Chest. 95 (6): 1316–1318. doi:10.1378/chest.95.6.1316. PMID 2721271.
14. Danilova V, Hellekant G (2003). "Comparison of the responses of the chorda tympani and glossopharyngeal nerves to taste stimuli in C57BL/6J mice". BMC Neuroscience. 4: 5–6. doi:10.1186/1471-2202-4-5. PMC 153500. PMID 12617752.

Further reading

• Chandrashekar J, Hoon MA, Ryba NJ, Zuker CS (2007). "The receptors and cells for mammalian taste". Nature. 444 (7117): 288–94. Bibcode:2006Natur.444..288C. doi:10.1038/nature05401. PMID 17108952.
• 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. PMID 11326277.
• Nelson G, Chandrashekar J, Hoon MA, Feng L, Zhao G, Ryba NJ, Zuker CS (2002). "An amino-acid taste receptor". Nature. 416 (6877): 199–202. Bibcode:2002Natur.416..199N. doi:10.1038/nature726. PMID 11894099.
• Li X, Staszewski L, Xu H, Durick K, Zoller M, Adler E (2002). "Human receptors for sweet and umami taste". Proc. Natl. Acad. Sci. U.S.A. 99 (7): 4692–6. Bibcode:2002PNAS...99.4692L. doi:10.1073/pnas.072090199. PMC 123709. PMID 11917125.
• 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. PMID 12706725.
• 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. PMID 12892531.
• 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. PMID 15299024.
• Xu H, Staszewski L, Tang H, Adler E, Zoller M, Li X (2005). "Different functional roles of T1R subunits in the heteromeric taste receptors". Proc. Natl. Acad. Sci. U.S.A. 101 (39): 14258–63. Bibcode:2004PNAS..10114258X. doi:10.1073/pnas.0404384101. PMC 521102. PMID 15353592.
• 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. PMID 15585941.
• 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. PMID 15668251.
• Galindo-Cuspinera V, Winnig M, Bufe B, Meyerhof W, Breslin PA (2006). "A TAS1R receptor-based explanation of sweet 'water-taste'". Nature. 441 (7091): 354–7. Bibcode:2006Natur.441..354G. doi:10.1038/nature04765. PMID 16633339.
• 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. PMID 16720576.
• 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. PMID 17499612.
• Mosinger B, Redding KM, Parker MR, Yevshayeva V, Yee KK, Dyomina K, Li Y, Margolskee RF (2013). "Genetic loss or pharmacological blockade of testes-expressed taste genes causes male sterility". Proceedings of the National Academy of Sciences of the United States of America. 110 (30): 12319–24. Bibcode:2013PNAS..11012319M. doi:10.1073/pnas.1302827110. PMC 3725061. PMID 23818598.

External links

• TAS1R3 Gene
• TASTE RECEPTOR TYPE 1, MEMBER 3; TAS1R3

This article incorporates text from the United States National Library of Medicine, which is in the public domain.