Advertisement

Mammalian Genome

, Volume 14, Issue 5, pp 291–301 | Cite as

Three sweet receptor genes are clustered in human Chromosome 1

  • Jiayu LiaoEmail author
  • Peter G. Schultz
Article

Abstract

A search of the human genome database led us to identify three human candidate taste receptors, hT1R1, hT1R2, and hT1R3, which contain seven transmembrane domains. All three genes map to a small region of Chromosome (Chr) 1. This region is syntenous to the distal end of Chr 4 in mouse, which contains the Sac (saccharin preference) locus that is involved in detecting sweet tastants. A genetic marker, DVL1, which is linked to the Sac locus, is within 1700 bp of human T1R3. Recently, the murine T1Rs and its human ortholog have been independently identified in combination as sweet and umami receptors near the Sac locus. All three hT1Rs genes are expressed selectively in human taste receptor cells in the fungiform papillae, consistent with their role in taste perception.

Keywords

Taste Receptor Taste Cell Taste Receptor Cell Fungiform Papilla Human Genome Database 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

We thank A. Patapoutian and M. Cooke for comments and helpful discussions. We also thank A. Moqrich and G. Story for help with the in situ hybridizations and the bioinformatics group at GNF for computational support. We are particularly indebted to J. Watson for preparing sections for us. We are particularly grateful to F. Lippincott and T.Wiltshire for their help with DNA sequencing. We also thank D. Ly for his help in obtaining human tongue for us. This work was supported in part by the Novartis Research Foundation. This is manuscript number 14362-CH of The Scripps Research Institute.

References

  1. 1.
    Adler, E, Hoon, MA, Mueller, KL, Chandrashekar, J, Ryba, NJP,  et al. 2000A novel family of mammalian taste receptors.Cell100693702PubMedGoogle Scholar
  2. 2.
    Akabas, MH, Dodd, J, Al-Awqati, Q 1988A bitter substance induces a rise in intracellular calcium in a subpopulation of rat taste cells.Science24210471050PubMedGoogle Scholar
  3. 3.
    Avenet, P, Lindemann, B 1988Amiloride-blockable sodium currents in isolated taste receptor cells.J Membr Biol105245255PubMedGoogle Scholar
  4. 4.
    Bachmanov, A 1997Sucrose consumption in mice: major influence of two genetic loci affecting peripheral sensory responses.Mamm Genome8545548CrossRefPubMedGoogle Scholar
  5. 5.
    Bachmanov, AA, Reed, DR, Ninomiya, Y, Inoue, M, Tordoff, MG 1997Sucrose consumption in mice: major influence of two genetic loci affecting peripheral sensory responses.Mamm Genome8545548CrossRefPubMedGoogle Scholar
  6. 6.
    Bachmanov, AA, Li, X, Reed, DR, Ohmen, JD, Li, S,  et al. 2001Positional cloning of the mouse saccharin preference (Sac) locus.Chem Senses26925933CrossRefPubMedGoogle Scholar
  7. 7.
    Bernhardt, SJ, Naim, M, Zehavi, U, Lindemann, B 1996Changes in IP3 and cytosolic Ca2+ in response to sugars and non-sugar sweeteners in transduction of sweet taste in the rat.J Physiol490325336PubMedGoogle Scholar
  8. 8.
    Brown, EM, Gmba, G, Roccardi, D, Lombardi, M, Butters, R,  et al. 1993Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid.Nature366575580Google Scholar
  9. 9.
    Buck, L 2000The molecular architecture of odor and pheromone sensing in mammals.Cell100611618PubMedGoogle Scholar
  10. 10.
    Capeless, C, Whitney, G 1995The 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 Senses20291298PubMedGoogle Scholar
  11. 11.
    Chandrashekar, J, Mueller, KL, Hoon, MA, Adler, E, Feng, L,  et al. 2000T2Rs function as bitter taste receptors.Cell100703711PubMedGoogle Scholar
  12. 12.
    Chaudharri, N, Landin, AM, Roper, SD 2000A metabotropic glutamate receptor variant functions as a taste receptor.Nature Neurosci3113119CrossRefPubMedGoogle Scholar
  13. 13.
    Doolin, RE, Gibertson, TA 1996Distribution and characterization of functional amiloride-sensitive sodium channels in rat tongue.J Gen Physiol107545554PubMedGoogle Scholar
  14. 14.
    Firestein, S 2000The good taste of genomics.Nature404552553CrossRefPubMedGoogle Scholar
  15. 15.
    Formaker, BK, Hill, DL 1988An analysis of residual NaCl taste response after amiloride.Am J Physiol25510021007Google Scholar
  16. 16.
    Froloff, N, Faurion, A, MacLeod, P 1996Multiple human taste receptor sites: a molecular modeling approach.Chem Senses21425445PubMedGoogle Scholar
  17. 17.
    Fuller, J 1974Single-locus control of saccharin preference in mice.J Hered653336PubMedGoogle Scholar
  18. 18.
    Gilbertson, TA, Avenet, P, Kinnamon, SC, Roper, SD 1992Proton currents through amiloride-sensitive Na channels in hamster taste cells. Role in acid transduction.J Gen Physiol100803824PubMedGoogle Scholar
  19. 19.
    Gilbertson, T, Damak, S, Margolskee, R 2000The molecular physiology of taste transduction.Curr Opin Neurobiol10519527Google Scholar
  20. 20.
    Glaser, D, Tinti, JM, Nofre, C 1995Evolution 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 Senses20573584PubMedGoogle Scholar
  21. 21.
    Heck, GL, Mierson, S, DeSimone, JA 1984Salt taste transduction occurs through an amiloride-sensitive sodium transport pathway.Science223403405PubMedGoogle Scholar
  22. 22.
    Hoon, MA, Northup, JK, Margolskee, RF 1995Functional expression of the taste specific G-protein, alpha-gustducin.Biochem J309629636PubMedGoogle Scholar
  23. 23.
    Hoon, MA, Adler, E, Lindemeier, J, Battey, JF, Ryba, NJP,  et al. 1999Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity.Cell96541551PubMedGoogle Scholar
  24. 24.
    Kinnamon, SC, Cummings, TA 1992Chemosensory transduction mechanisms in taste.Annu Rev Physiol54715731CrossRefPubMedGoogle Scholar
  25. 25.
    Kinnamon, SC, Dionne, VE, Beam, KG 1988Apical localization of K+ channels in taste cells provides the basis for sour taste transduction.Proc Natl Acad Sci USA8570237027PubMedGoogle Scholar
  26. 26.
    Kitagawa, M, Kusakabe, Y, Miura, H, Ninomiya, Y, Hina, A 2001Molecular genetic identification of a candidate receptor gene for sweet taste.Biochem Biophys Res Commun283236242CrossRefPubMedGoogle Scholar
  27. 27.
    Kunishima, N, Shimada, Y, Tsuji, Y, Sato, T, Yamamoto, M,  et al. 2000Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.Nature407971977Google Scholar
  28. 28.
    Li, X, Inoue, M, Reed, DR, Huque, T, Puchalski, RB,  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 Genome121316Google Scholar
  29. 29.
    Li, X, Staszewski, L, Xu, H, Durick, K, Zoller, M,  et al. 2002Human receptors for sweet and umami taste.Proc Natl Acad Sci USA9946924696CrossRefPubMedGoogle Scholar
  30. 30.
    Lindemann, B 1996Taste reception.Physiol Rev76718766PubMedGoogle Scholar
  31. 31.
    Lush, IE 1989The genetics of tasting in mice. VI. Saccharin, acesulfame, dulcin and sucrose.Genet Res539599PubMedGoogle Scholar
  32. 32.
    Lush, I, Hornigold, N, King, P, Stoye, J 1995The genetics of tasting in mice. VII. Glycine revisited, and the chromosomal location of Sac and Soa.Genet Res66167174PubMedGoogle Scholar
  33. 33.
    Matsunami, H, Buck, LB 1997A multigene family encoding a diverse array of putative pheromone receptors in mammals.Cell90775784PubMedGoogle Scholar
  34. 34.
    Matsunami, H, Montmayeur, JP, Buck, LB 2000A family of candidate taste receptors in human and mouse.Nature404601603CrossRefPubMedGoogle Scholar
  35. 35.
    Max, M, Shanker, YG, Huang, L, Rong, M, Liu, Z,  et al. 2001Tas13, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac.Nat Genet285863CrossRefPubMedGoogle Scholar
  36. 36.
    Montmayeur, JP, Liberles, SD, Matsunami, H, Buck, LB 2001A candidate taste receptor gene near a sweet taste locus.Nat Neurosci4492498PubMedGoogle Scholar
  37. 37.
    Nelson, G, Hoon, MA, Chandrashekar, J, Zhang, Y, Ryba, NJP,  et al. 2001Mammalian sweet taste receptors.Cell106381390PubMedGoogle Scholar
  38. 38.
    Sainz, E, Korley, JN, Battey, JF, Sullivan, SL 2001Identification of a novel member of the T1R family of putative taste receptors.J Neurochem77896903CrossRefPubMedGoogle Scholar
  39. 39.
    Schiffman, S, Cahn, H, Lindley, M 1981Multiple receptor sites mediate sweetness: evidence from cross adaptation.Pharmacol Biochem Behav15377388CrossRefPubMedGoogle Scholar
  40. 40.
    Spielman, AL, Nagai, H, Sunnavala, G, Dasso, M, Breer, H,  et al. 1996Rapid kinetics of second messenger production in bitter taste.Am J Physiol270C926C931PubMedGoogle Scholar
  41. 41.
    Striem, BJ, Pace, U, Zehavi, U, Naim, M, Lancet, D 1989Sweet tastants stimulate adenylate cyclase coupled to GTP-binding protein in rat tongue membranes.Biochem J260121126PubMedGoogle Scholar
  42. 42.
    Reed, D 2000Gene mapping for taste related phenotypes in humans and mice.Appetite35189190CrossRefPubMedGoogle Scholar
  43. 43.
    Ruiz-Avila, L, Mckinnon, PJ, Wildman, D, Mckinnon, PJ, Robichon, A,  et al. 1995Coupling of bitter receptor to phosphodiesterase through transducin in taste receptor cells.Nature3768085CrossRefPubMedGoogle Scholar
  44. 44.
    Tonosaki, K, Funakoshi, M 1989Cross-adapted sugar responses in the mouse taste cell.Comp Biochem Physiol92A181183CrossRefGoogle Scholar
  45. 45.
    Wong, GT, Gannon, KS, Margolskee, RF 1996Transduction of bitter and sweet taste by gustducin.Nature381796800PubMedGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 2003

Authors and Affiliations

  1. 1.Department of Chemistry and the Skaggs Institute for Chemical BiologyThe Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037USA
  2. 2.The Genomic Institute of the Novartis Research Foundation, 3115 Merryfield Row, Suit 200, San Diego, California 92121USA

Personalised recommendations