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Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac

Nature Genetics volume 28, pages 58–63 (2001)Cite this article

Abstract

The ability to taste the sweetness of carbohydrate-rich foodstuffs has a critical role in the nutritional status of humans. Although several components of bitter transduction pathways have been identified1,2,3,4,5,6, the receptors and other sweet transduction elements remain unknown. The Sac locus in mouse, mapped to the distal end of chromosome 4 (refs. 7–9), is the major determinant of differences between sweet-sensitive and -insensitive strains of mice in their responsiveness to saccharin, sucrose and other sweeteners10,11,12,13. To identify the human Sac locus, we searched for candidate genes within a region of approximately one million base pairs of the sequenced human genome syntenous to the region of Sac in mouse. From this search, we identified a likely candidate: T1R3, a previously unknown G protein-coupled receptor (GPCR) and the only GPCR in this region. Mouse Tas1r3 (encoding T1r3) maps to within 20,000 bp of the marker closest to Sac (ref. 9) and, like human TAS1R3, is expressed selectively in taste receptor cells. By comparing the sequence of Tas1r3 from several independently derived strains of mice, we identified a specific polymorphism that assorts between taster and non-taster strains. According to models of its structure, T1r3 from non-tasters is predicted to have an extra amino-terminal glycosylation site that, if used, would interfere with dimerization.

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Figure 1: Candidate genes in the region of the Sac locus.
Figure 2: Expression of Tas1r3 mRNA in mouse tissues and mouse taste cells.
Figure 3: Co-localization of T1R3, PLCβ2 and α-gustducin in human taste receptor cells.
Figure 4: Tas1r3 allelic differences.
Figure 5: The amino acid sequence of T1r3 is aligned with that of two rat taste receptors (rT1R1 and rT1R2), the mouse extracellular calcium sensing (mECaSR) and the metabotropic glutamate type 1 (mGluR1) receptors.
Figure 6: The predicted three-dimensional structure of the N-terminal domain of T1r3. The model shows a homodimer of T1r3.

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Acknowledgements

We thank S. Zou for DNA sequencing; D. Perl and the staff of the MSSM Pathology Department for human taste tissue; and I. Visiers for help with modeling the structure of T1r3. This research was supported by grants from the NIH: DC03155 (R.F.M.), MH57241 (M.M.) and DC00310 (L.H.).

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Author notes

  1. Marianna Max and Y. Gopi Shanker: These authors contributed equally to this work.

Authors and Affiliations

  1. Howard Hughes Medical Institute, Mount Sinai School of Medicine of New York University, New York, New York, USA

    Y. Gopi Shanker, Liquan Huang, Minqing Rong, Zhan Liu & Robert F. Margolskee

  2. Department of Physiology and Biophysics, Mount Sinai School of Medicine of New York University, New York, New York, USA

    Marianna Max, Y. Gopi Shanker, Liquan Huang, Minqing Rong, Zhan Liu, Fabien Campagne, Harel Weinstein, Sami Damak & Robert F. Margolskee

  3. Institute for Computational Biomedicine, Mount Sinai School of Medicine of New York University, New York, New York, USA

    Fabien Campagne & Harel Weinstein

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  1. Marianna Max
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Correspondence to Robert F. Margolskee.

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Max, M., Shanker, Y., Huang, L. et al. Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac. Nat Genet 28, 58–63 (2001). https://doi.org/10.1038/ng0501-58

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