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A candidate taste receptor gene near a sweet taste locus

Abstract

The mechanisms underlying sweet taste in mammals have been elusive. Although numerous studies have implicated G proteins in sweet taste detection, the expected G protein-coupled receptors have not been found. Here we describe a candidate taste receptor gene, T1r3, that is located at or near the mouse Sac locus, a genetic locus that controls the detection of certain sweet tastants. T1R3 differs in amino acid sequence in mouse strains with different Sac phenotypes ('tasters' versus 'nontasters'). In addition, a perfect correlation exists between two different T1r3 alleles and Sac phenotypes in recombinant inbred mouse strains. The T1r3 gene is expressed in a subset of taste cells in circumvallate, foliate and fungiform taste papillae. In circumvallate and foliate papillae, most T1r3-expressing cells also express a gene encoding a related receptor, T1R2, raising the possibility that these cells recognize more than one ligand, or that the two receptors function as heterodimers.

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Figure 1: T1R3 differs in mice with different Sac phenotypes.
Figure 2: The mT1r3 gene is located near the Sac locus on mouse chromosome 4.
Figure 3: Polymorphisms in the T1r3 gene are correlated with Sac phenotypes.
Figure 4: The pattern of expression of T1r3 differs from that of T1r1 and T1r2.
Figure 5: T1r3 is coexpressed with T1r2, but not gustducin.

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References

  1. Lindemann, B. Taste reception. Physiol. Rev. 76, 718–766 (1996).

    Article  Google Scholar 

  2. Herness, M. S. & Gilbertson, T. A. Cellular mechanisms of taste transduction. Annu. Rev. Physiol. 61, 873–900 (1999).

    Article  CAS  PubMed  Google Scholar 

  3. Gilbertson, T., Damak, S. & Margolskee, R. The molecular physiology of taste transduction. Curr. Opin. Neurobiol. 10, 519–527 (2000).

    Article  CAS  PubMed  Google Scholar 

  4. Wong, G. T., Gannon, K. S. & Margolskee, R. F. Transduction of bitter and sweet taste by gustducin. Nature 381, 796–800 (1996).

    Article  CAS  PubMed  Google Scholar 

  5. Kinnamon, S. A plethora of taste receptors. Neuron 25, 507–510 (2000).

    Article  CAS  PubMed  Google Scholar 

  6. Chaudhari, N., Landin, A. & Roper, S. A metabotropic glutamate receptor variant functions as a taste receptor. Nat. Neurosci. 3, 113–119 (2000).

    Article  CAS  PubMed  Google Scholar 

  7. Adler, E. et al. A novel family of mammalian taste receptors. Cell 100, 693–702 (2000).

    Article  CAS  PubMed  Google Scholar 

  8. Matsunami, H., Montmayeur, J.-P. & Buck, L. A family of candidate taste receptors in human and mouse. Nature 404, 601–604 (2000).

    Article  CAS  PubMed  Google Scholar 

  9. Chandrashekar, J. et al. T2Rs function as bitter taste receptors. Cell 100, 703–711 (2000).

    Article  CAS  PubMed  Google Scholar 

  10. Ishimoto, H., Matsumoto, A. & Tanimura, T. Molecular identification of a taste receptor gene for trehalose in Drosophila. Science 289, 116–119 (2000).

    Article  CAS  PubMed  Google Scholar 

  11. Hoon, M. A. et al. Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity. Cell 96, 541–551 (1999).

    Article  CAS  PubMed  Google Scholar 

  12. Reed, D. Gene mapping for taste related phenotypes in human and mice. Appetite 35, 189–190 (2000).

    Article  CAS  PubMed  Google Scholar 

  13. Fuller, J. Single-locus control of saccharin preference in mice. J. Hered. 65, 33–36 (1974).

    Article  CAS  PubMed  Google Scholar 

  14. Lush, I. The genetics of tasting in mice: VI. Saccharin, acesulfame, dulcin and sucrose. Genet. Res. 53, 95–99 (1989).

    Article  CAS  PubMed  Google Scholar 

  15. Lush, I., Hornigold, N., King, P. & Stoye, J. The genetics of tasting in mice. VII. Glycine revisited, and the chromosomal location of Sac and Soa. Genet. Res. 66, 167–174 (1995).

    Article  CAS  PubMed  Google Scholar 

  16. Capeless, C. & Whitney, G. The genetic basis of preference for sweet substances among inbred strains of mice: Preference ratio phenotypes and the alleles of the Sac and dpa loci. Chem. Senses 20, 291–298 (1995).

    Article  CAS  PubMed  Google Scholar 

  17. Bachmanov, A. et al. Sucrose consumption in mice: major influence of two genetic loci affecting peripheral sensory responses. Mamm. Genome 8, 545–548 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Blizard, D., Kotlus, B. & Frank, M. Quantitative trait loci associated with short-term intake of sucrose saccharin and quinine solutions in laboratory mice. Chem. Senses 24, 373–385 (1999).

    Article  CAS  PubMed  Google Scholar 

  19. Belknap, J. et al. Single locus control of saccharin intake in BXD/Ty recombinant inbred (RI) mice: some methodological implications for RI strain analysis. Behav. Genet. 22, 81–100 (1992).

    Article  CAS  PubMed  Google Scholar 

  20. Frank, M. & Blizard, D. Chorda tympani responses in two inbred strains of mice with different taste preferences. Physiol. Behav. 67, 287–297 (1999).

    Article  CAS  PubMed  Google Scholar 

  21. Brown, E. et al. Cloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroid. Nature 366, 575–580 (1993).

    Article  CAS  PubMed  Google Scholar 

  22. Herrada, G. & Dulac, C. A novel family of putative pheromone receptors in mammals with a topographically organized and sexually dimorphic distribution. Cell 90, 763–773 (1997).

    Article  CAS  PubMed  Google Scholar 

  23. Matsunami, H. & Buck, L. A multigene family encoding a diverse array of putative pheromone receptors in mammals. Cell 90, 775–784 (1997).

    Article  CAS  PubMed  Google Scholar 

  24. Ryba, N. J. & Tirindelli, R. A new multigene family of putative pheromone receptors. Neuron 19, 371–379 (1997).

    Article  CAS  PubMed  Google Scholar 

  25. Takahashi, K., Tsuchida, K., Tanabe, Y., Masu, M. & Nakanishi, S. Role of the large extracellular domain of metabotropic glutamate receptors in agonist selectivity determination. J. Biol. Chem. 268, 19341–19345 (1993).

    CAS  PubMed  Google Scholar 

  26. Kunishima, N. et al. Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor. Nature 407, 971–977 (2000).

    Article  CAS  PubMed  Google Scholar 

  27. McCarthy, L. et al. A first-generation whole genome-radiation hybrid map spanning the mouse genome. Genome Res. 7, 1153–1161 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Eicher, E. & Shown, E. Molecular markers that define the distal end of mouse autosomes 4, 13, and 19 and the sex chromosomes. Mamm. Genome 4, 226–229 (1993).

    Article  CAS  PubMed  Google Scholar 

  29. Danciger, M., Farber, D., Peyser, M. & Kozak, C. The gene for the beta-subunit of retinal transducin (Gnb-1) maps to distal mouse chromosome 4, and related sequences map to mouse chromosomes 5 and 8. Genomics 6, 428–435 (1990).

    Article  CAS  PubMed  Google Scholar 

  30. Greenfield, A., Brown, S., Friedman, J. & Bahary, N. Mapping of clone D4Smh6b to the distal end of mouse chromosome 4. Mouse Genome 90, 94–95 (1992).

    Google Scholar 

  31. Li, X. et al. High-resolution genetic mapping of the saccharin preference locus (Sac) and the putative sweet taste receptor (T1R1) gene (Gpr70 ) to mouse distal Chromosome 4. Mamm. Genome 12, 13–16 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Bai, M. Structure and function of the extracellular calcium-sensing receptor. Intl. J. Mol. Med. 4, 115–125 (1999).

    CAS  Google Scholar 

  33. Pelz, W., Whitney, G. & Smith, J. Genetic influences on saccharin preference of mice. Physiol. Behav. 10, 263–265 (1973).

    Article  CAS  PubMed  Google Scholar 

  34. Ramirez, I. & Fuller, J. Genetic influence on water and sweetened water consumption in mice. Physiol. Behav. 16, 163–168 (1976).

    Article  CAS  PubMed  Google Scholar 

  35. Ruiz-Avila, L. et al. Coupling of bitter receptor to phosphodiesterase through transducin in taste receptor cells. Nature 376, 80–85 (1995).

    Article  CAS  PubMed  Google Scholar 

  36. Ming, D., Ruiz-Avila, L. & Margolskee, R. Characterization and solubilization of bitter-responsive receptors that couple to gustducin. Proc. Natl. Acad. Sci. USA 95, 8933–8938 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Marshall, F., Jones, K., Kaupmann, K. & Bettler, B. GABAB receptors—the first 7TM heterodimers. Trends Pharmacol. Sci. 20, 396–399 (1999).

    Article  CAS  PubMed  Google Scholar 

  38. Bernhardt, S., Naim, M., Zehavi, U. & Lindemann, B. Changes in IP3 and cytosolic Ca2+ in response to sugars and non-sugar sweeteners in transduction of sweet taste in the rat. J. Physiol. (Lond.) 490, 325–336 (1996).

    Article  CAS  Google Scholar 

  39. Gimelbrant, A., Haley, S. & McClintock, T. Olfactory receptor trafficking involves conserved regulatory steps. J. Biol. Chem. 276, 7285–7290 (2001).

    Article  CAS  PubMed  Google Scholar 

  40. Faurion, A., Saito, S. & Mac Leod, P. Sweet taste involves several distinct receptor mechanisms. Chem. Senses 5, 107–121 (1980).

    Article  CAS  Google Scholar 

  41. Glaser, D., Tinti, J.-M. & Nofre, C. Evolution of the sweetness receptor in primates. I. Why does alitame taste sweet in all prosimians and simians, and aspartame only in old world simians? Chem. Senses 20, 573–584 (1995).

    Article  CAS  PubMed  Google Scholar 

  42. Nofre, C., Tinti, J.-M. & Glaser, D. Evolution of the sweetness receptor in primates. II. Gustatory responses of non-human primates to nine compounds known to be sweet in man. Chem. Senses 21, 747–762 (1996).

    Article  CAS  PubMed  Google Scholar 

  43. Froloff, N., Faurion, A. & Mac Leod, P. Multiple human taste receptor sites: a molecular modeling approach. Chem. Senses 21, 425–445 (1996).

    Article  CAS  PubMed  Google Scholar 

  44. Nimomiya, Y., Inoue, M., Imoto, T. & Nakashima, K. Lack of gurmarin sensitivity of sweet taste receptors innervated by the glossopharyngeal nerve in C57BL mice. Am. J. Physiol. 272, R1002–R1006 (1997).

    Google Scholar 

  45. Nimomiya, Y., Imoto, T. & Sugimura, T. Sweet taste response of mouse chorda tympani neurons: Existence of gurmarin-sensitive and -insensitive receptor components. J. Neurophysiol. 81, 3087–3091 (1999).

    Article  Google Scholar 

  46. Schiffman, S., Cahn, H. & Lindley, M. Multiple receptor sites mediate sweetness: evidence from cross adaptation. Pharmacol. Biochem. Behav. 15, 377–388 (1981).

    Article  CAS  PubMed  Google Scholar 

  47. Froloff, N., Lloret, E., Martinez, J.-M. & Faurion, A. Cross-adaptation and molecular modeling study of receptor mechanisms common to four taste stimuli in humans. Chem. Senses 23, 197–206 (1998).

    Article  CAS  PubMed  Google Scholar 

  48. Tonosaki, K. & Funakoshi, M. Cross-adapted sugar responses in the mouse taste cell. Comp. Biochem. Physiol. 92A, 181–183 (1989).

    Article  CAS  Google Scholar 

  49. Berghard, A. & Buck, L. Sensory transduction in vomeronasal neurons: evidence for G alpha o, G alpha i2, and adenylyl cyclase II as major components of a pheromone signaling cascade. J. Neurosci. 16, 909–918 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Malnic, B., Hirono, J., Sato, T. & Buck, L.B. Combinatorial receptor codes for odors. Cell 96, 713–723 (1999).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank L. Rowe at The Jackson Laboratory for suggestions and contributions to the chromosome mapping studies. We also thank C. Gao for technical assistance, and members of the Buck lab, in particular, C. Neophytou, for help, comments and discussions throughout this project. This work was supported by the Howard Hughes Medical Institute, grants from the National Institutes of Health (L.B.B.), and fellowship support from the Alice and Joseph Brook Fund (J.-P.M.), the Naito Foundation (H.M.), and the Japan Society for the Promotion of Science (H.M.). GenBank accession number for mT1R1, mT1R2 and mT1R3 are AF337039-41

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Montmayeur, JP., Liberles, S., Matsunami, H. et al. A candidate taste receptor gene near a sweet taste locus. Nat Neurosci 4, 492–498 (2001). https://doi.org/10.1038/87440

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