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PubMed · 10761935

T2Rs function as bitter taste receptors.

J Chandrashekar·K L Mueller·M A Hoon·E Adler·L Feng·W Guo·C S Zuker·N J Ryba
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Abstract

Bitter taste perception provides animals with critical protection against ingestion of poisonous compounds. In the accompanying paper, we report the characterization of a large family of putative mammalian taste receptors (T2Rs). Here we use a heterologous expression system to show that specific T2Rs function as bitter taste receptors. A mouse T2R (mT2R-5) responds to the bitter tastant cycloheximide, and a human and a mouse receptor (hT2R-4 and mT2R-8) responded to denatonium and 6-n-propyl-2-thiouracil. Mice strains deficient in their ability to detect cycloheximide have amino acid substitutions in the mT2R-5 gene; these changes render the receptor significantly less responsive to cycloheximide. We also expressed mT2R-5 in insect cells and demonstrate specific tastant-dependent activation of gustducin, a G protein implicated in bitter signaling. Since a single taste receptor cell expresses a large repertoire of T2Rs, these findings provide a plausible explanation for the uniform bitter taste that is evoked by many structurally unrelated toxic compounds.

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Afferent PathwaysAmino Acid SequenceAnimalsCalciumCell LineChemoreceptor CellsCycloheximideGene ExpressionHumansKidneyMiceMice, Inbred C57BLMice, Inbred DBAMolecular Sequence DataProtein Synthesis InhibitorsQuaternary Ammonium CompoundsReceptors, Cell SurfaceReceptors, G-Protein-CoupledRecombinant Fusion ProteinsSignal TransductionTasteTaste BudsTransducinTransfectionTaste Receptors, Type 2Journal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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J Chandrashekar, K L Mueller, M A Hoon, E Adler, L Feng, W Guo, C S Zuker, N J Ryba. 2000-03-17. T2Rs function as bitter taste receptors.. https://doi.org/10.1016/s0092-8674(00)80706-0

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