The sense of taste provides animals with valuable information about the nature and quality of food. Bitter taste detection functions as an important sensory input to warn against the ingestion of toxic and noxious substances. T2Rs are a family of approximately 30 highly divergent G-protein-coupled receptors (GPCRs)1,2 that are selectively expressed in the tongue and palate epithelium1 and are implicated in bitter taste sensing1,2,3,4,5,6,7,8. Here we demonstrate, using a combination of genetic, behavioural and physiological studies, that T2R receptors are necessary and sufficient for the detection and perception of bitter compounds, and show that differences in T2Rs between species (human and mouse) can determine the selectivity of bitter taste responses. In addition, we show that mice engineered to express a bitter taste receptor in ‘sweet cells’9 become strongly attracted to its cognate bitter tastants, whereas expression of the same receptor (or even a novel GPCR) in T2R-expressing cells resulted in mice that are averse to the respective compounds. Together these results illustrate the fundamental principle of bitter taste coding at the periphery: dedicated cells act as broadly tuned bitter sensors that are wired to mediate behavioural aversion.
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We thank F. Liu for help generating T2R5 knockout animals. We are also grateful to A. Cho and S. Taduru for generation of transgenic lines, and to A. Leslie for preparation of antibodies. We thank members of the Zuker and Ryba laboratories for valuable comments and advice. This work was supported in part by a grant from the National Institute on Deafness and Other Communication Disorders to C.S.Z. C.S.Z. is an investigator of the Howard Hughes Medical Institute.
The authors declare that they have no competing financial interests.
This file contains the figure legends for Supplementary Figures 1-3. (DOC 22 kb)
T2R5-/- construct and physiology. (PDF 84 kb)
T2R5-/- mice respond normally to a variety of bitter, sweet, umami, salty and sour stimuli. (PDF 56 kb)
T2R cells mediate bitter but not sweet or umami taste. (PDF 77 kb)
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Mueller, K., Hoon, M., Erlenbach, I. et al. The receptors and coding logic for bitter taste. Nature 434, 225–229 (2005). https://doi.org/10.1038/nature03352
Journal of Translational Medicine (2021)
Cellular and Molecular Life Sciences (2021)
Cell and Tissue Research (2021)