T2Rs function as bitter taste receptors.
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.
Chandrashekar
J
J
Howard Hughes Medical Institute and Department of Biology, University of California, San Diego, La Jolla 92093, USA.
Mueller
K L
KL
Hoon
M A
MA
Adler
E
E
Feng
L
L
Guo
W
W
Zuker
C S
CS
Ryba
N J
NJ
D000344:Afferent Pathways / Q000737:chemistry / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000032:analysis; D002460:Cell Line; D002628:Chemoreceptor Cells / Q000737:chemistry* / Q000502:physiology; D003513:Cycloheximide; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D011500:Protein Synthesis Inhibitors; D000644:Quaternary Ammonium Compounds; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013649:Taste / Q000502:physiology*; D013650:Taste Buds / Q000737:chemistry* / Q000502:physiology; D015293:Transducin / Q000378:metabolism; D014162:Transfection; D000098706:Taste Receptors, Type 2
D002118:Calcium; D003513:Cycloheximide; D011500:Protein Synthesis Inhibitors; D000644:Quaternary Ammonium Compounds; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D015293:Transducin; D000098706:Taste Receptors, Type 2; C075192:gustducin; C043414:denatonium