Taste

Abstract: The sense of taste provides animals with valuable information about the nature and quality of food. Mammals can recognize and respond to a diverse repertoire of chemical entities, including sugars, salts, acids and a wide range of toxic substances. Several amino acids taste sweet or delicious (umami) to humans, and are attractive to rodents and other animals. This is noteworthy because L-amino acids function as the building blocks of proteins, as biosynthetic precursors of many biologically relevant small molecules, and as metabolic fuel. Thus, having a taste pathway dedicated to their detection probably had significant evolutionary implications. Here we identify and characterize a mammalian amino-acid taste receptor. This receptor, T1R1+3, is a heteromer of the taste-specific T1R1 and T1R3 G-protein-coupled receptors. We demonstrate that T1R1 and T1R3 combine to function as a broadly tuned L-amino-acid sensor responding to most of the 20 standard amino acids, but not to their D-enantiomers or other compounds. We also show that sequence differences in T1R receptors within and between species (human and mouse) can significantly influence the selectivity and specificity of taste responses.

Abstract: Bitter taste perception provides animals with critical genetics, expression profile, and diversity of the T2R protection against ingestion of poisonous compounds. family support the proposal that T2Rs are taste recepIn the accompanying paper, we report the character- tors, rigorous demonstration of their role in taste transization of a large family of putative mammalian taste duction requires functional validation. Here we use a receptors (T2Rs). Here we use a heterologous expres- heterologous expression system to demonstrate that sion system to show that specific T2Rs function as T2Rs function as receptors for bitter tastants. We anabitter taste receptors. A mouse T2R (mT2R-5) re- lyzed mouse strains that differ in their recognition of sponds to the bitter tastant cycloheximide, and a hu- various bitter compounds and show that mice that do man and a mouse receptor (hT2R-4 and mT2R-8) re- not perceive low concentrations of cycloheximide consponded to denatonium and 6-n-propyl-2-thiouracil. tain missense mutations in the mT2R-5 gene. These Mice strains deficient in their ability to detect cyclo- amino acid changes significantly reduce the sensitivity heximide have amino acid substitutions in the mT2R-5 of the mT2R-5 receptor to cycloheximide. Notably, this gene; these changes render the receptor significantly sensitivity shift measured in cell-based assays closely less responsive to cycloheximide. We also expressed mirrors the behavioral phenotype of the Cyx-deficient mT2R-5 in insect cells and demonstrate specific tast- mice (Lush and Holland, 1988). The discovery of mamant-dependent activation of gustducin, a G protein im- malian bitter receptors will help understand the biology plicated in bitter signaling. Since a single taste recep- of bitter perception, from transduction pathways in retor cell expresses a large repertoire of T2Rs, these ceptor cells to coding of bitter signals through the afferfindings provide a plausible explanation for the uni- ent sensory pathway. form bitter taste that is evoked by many structurally unrelated toxic compounds. Results and Discussion

Abstract: In mammals, taste perception is a major mode of sensory input. We have identified a novel family of 40-80 human and rodent G protein-coupled receptors expressed in subsets of taste receptor cells of the tongue and palate epithelia. These candidate taste receptors (T2Rs) are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. Notably, a single taste receptor cell expresses a large repertoire of T2Rs, suggesting that each cell may be capable of recognizing multiple tastants. T2Rs are exclusively expressed in taste receptor cells that contain the G protein alpha subunit gustducin, implying that they function as gustducin-linked receptors. In the accompanying paper, we demonstrate that T2Rs couple to gustducin in vitro, and respond to bitter tastants in a functional expression assay.

Abstract: The emerging picture of taste coding at the periphery is one of elegant simplicity. Contrary to what was generally believed, it is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes: sweet, sour, bitter, salty and umami. Importantly, receptor cells for each taste quality function as dedicated sensors wired to elicit stereotypic responses.

Abstract: Mammals can taste a wide repertoire of chemosensory stimuli. Two unrelated families of receptors (T1Rs and T2Rs) mediate responses to sweet, amino acids, and bitter compounds. Here, we demonstrate that knockouts of TRPM5, a taste TRP ion channel, or PLCbeta2, a phospholipase C selectively expressed in taste tissue, abolish sweet, amino acid, and bitter taste reception, but do not impact sour or salty tastes. Therefore, despite relying on different receptors, sweet, amino acid, and bitter transduction converge on common signaling molecules. Using PLCbeta2 taste-blind animals, we then examined a fundamental question in taste perception: how taste modalities are encoded at the cellular level. Mice engineered to rescue PLCbeta2 function exclusively in bitter-receptor expressing cells respond normally to bitter tastants but do not taste sweet or amino acid stimuli. Thus, bitter is encoded independently of sweet and amino acids, and taste receptor cells are not broadly tuned across these modalities.