The sense of taste is responsible for detecting and responding to sweet, bitter, sour, salty and umami (amino acid) stimuli. It is also capable of distinguishing between these various taste modalities to generate innate behavioral responses. For instance, animals are vigorously averse to bitter-tasting compounds, but are attracted to sweet and umami stimuli. In a wide ranging collaboration with Charles Zuker's group at UCSD, we have begun to define the components and the organization required for taste responses focusing primarily on the taste receptors themselves. These receptors provide powerful molecular tools to delineate the organization of the taste system, and to help define the logic of taste coding. We have identified and characterized two families of G-protein coupled receptors, the T1Rs and T2Rs. Using both model systems and knockout mice we have shown that the three T1Rs combine to generate the mammalian sweet and amino acid receptors. These attractive taste receptors are expressed in distinct subsets of taste receptor cells from the ~30 T2R bitter taste receptors. Using genetically modified animals we have shown that sweet, amino acid and bitter sensing cells share a common signaling pathway and are not broadly tuned across all modalities. These experiments also demonstrated that taste modalities function independently of each other. Importantly, our data have provided compelling evidence that taste receptor cells are tuned to respond to specific stimuli by virtue of the receptors that they express. However, it is activation of the cells rather than the receptors or indeed the tastants themselves that triggers stereotypic output: i.e. the sensation of sweet, bitter or umami taste. The critical next steps in deciphering the organization and function of the taste system are to define the cells and receptors responsible for sour and salty taste, and to map the connectivity pathways between taste receptor cells and afferent fibers.
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