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

doi:10.1016/s0092-8674(00)80706-0

T2Rs function as bitter taste receptors

Cell. 2000 Mar 17;100(6):703-11. doi: 10.1016/s0092-8674(00)80706-0.

Authors

J Chandrashekar¹, K L Mueller, M A Hoon, E Adler, L Feng, W Guo, C S Zuker, N J Ryba

Affiliation

¹ Howard Hughes Medical Institute and Department of Biology, University of California, San Diego, La Jolla 92093, USA.

PMID: 10761935
DOI: 10.1016/s0092-8674(00)80706-0

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Afferent Pathways / chemistry
Afferent Pathways / physiology
Amino Acid Sequence
Animals
Calcium / analysis
Cell Line
Chemoreceptor Cells / chemistry*
Chemoreceptor Cells / physiology
Cycloheximide
Gene Expression / physiology
Humans
Kidney / cytology
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Molecular Sequence Data
Protein Synthesis Inhibitors
Quaternary Ammonium Compounds
Receptors, Cell Surface / analysis
Receptors, Cell Surface / genetics*
Receptors, Cell Surface / metabolism*
Receptors, G-Protein-Coupled*
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Signal Transduction / physiology
Taste / physiology*
Taste Buds / chemistry*
Taste Buds / physiology
Transducin / metabolism
Transfection

Substances

Protein Synthesis Inhibitors
Quaternary Ammonium Compounds
Receptors, Cell Surface
Receptors, G-Protein-Coupled
Recombinant Fusion Proteins
taste receptors, type 2
gustducin
denatonium benzoate
Cycloheximide
Transducin
Calcium