A sweet beginning.

Animals have developed highly specialized sensory organs that detect physicochemical characteristics in the environment and translate this information into neuronal electrical activity. The coding of sensory stimuli into specific patterns of neuronal activity generates an internal representation of the external world that is processed by brain centers to elicit complex sensory perception and adapted behavioral responses. Major advances in the study of olfaction have resulted from the identification of genes encoding olfactory receptor molecules (see, for example2xBuck, L. and Axel, R. Cell. 1991; 65: 175–187Abstract | Full Text PDF | PubMed | Scopus (2085)See all References, 1xBuck, L. Annu. Rev. Neurosci. 1996; 19: 517–544Crossref | PubMedSee all References). Similarly, the recent characterization of novel genes encoding taste receptors will undoubtedly shed a new light on the logic of taste sensory processing.The sense of taste provides the animal with an immediate perception of food palatability: the hedonic perception of sweet, for example, signals highly caloric carbohydrate-rich nutrients, whereas potentially toxic substances such as plant alkaloids or cyanides elicit aversive bitterness. The initial event of taste recognition requires the activation of specific populations of taste receptor cells by tastant molecules. In mammals, onion-shaped clusters of taste receptor cells, the taste buds, are distributed within the different papillae of the tongue epithelium (see figure). Taste cells synapse with afferent nerve fibers connected to the gustatory nuclei in the brainstem, which in turn transmit sensory information to limbic and cortical brain areas. How are the diversity and specificity of the taste sensory response accomplished? Only five distinct gustatory perceptions have been identified in mammals: sweet, bitter, sour, salty, and umami (monosodium glutamate) (Linderman 1996xLinderman, B. Physiol. Rev. 1996; 76: 718–766PubMedSee all ReferencesLinderman 1996). Psychophysical studies have identified a coarse topographic organization of taste buds in distinct areas of the tongue according to preferential gustatory sensitivity (see figure). To a certain extent, however, all tastants can be detected throughout the tongue. In addition, although taste receptor cells are selectively activated by various tastants, individual taste cells and taste fibers are usually broadly tuned, showing sensory responses to several chemical stimuli (Frank 1973xFrank, M. J. Gen. Physiol. 1973; 61: 588–618Crossref | PubMedSee all ReferencesFrank 1973). A simple model of taste discrimination, according to which chemical stimuli from different modalities activate taste cells in topographically segregated areas of the tongue, is thus unlikely to be accurate.The characterization of candidate receptors for sweet and bitter by the groups of Zuker and of Ryba (Hoon et al. 1999xHoon, M.A., Adler, E., Lindemeier, J., Battey, J.F., Ryba, N.J.P., and Zuker, C.S. Cell. 1999; 96: 541–551Abstract | Full Text | Full Text PDF | PubMedSee all ReferencesHoon et al. 1999) is a new step toward the molecular analysis of taste information coding. Difference cloning has led to the isolation of a small family of genes encoding two novel seven transmembrane domain receptors, TR1 and TR2, that are likely to represent, respectively, the receptors for sweet and bitter tastants. Whereas TR1 transcripts are detected in all fungiform taste buds that preferentially respond to sweet stimuli, TR2, in contrast, is essentially undetectable in fungiform papillae but is present in taste buds of all circumvallate papillae, which are mostly sensitive to bitter substances. In accord with a function as taste receptors, TR1 and TR2 display a striking localization to the apical membrane of taste cells in the taste pore, where the detection of chemical stimuli is thought to occur. MoreoverHoon et al. 1999xHoon, M.A., Adler, E., Lindemeier, J., Battey, J.F., Ryba, N.J.P., and Zuker, C.S. Cell. 1999; 96: 541–551Abstract | Full Text | Full Text PDF | PubMedSee all ReferencesHoon et al. 1999 have demonstrated that TR1 and TR2 are virtually absent from cells expressing the G protein α subunit gustducin, although gustducin has been implicated into signal transduction of sweet and bitter tastants (Wong et al. 1996xWong, G.T., Gannon, K.S., and Margolskee, R.F. Nature. 1996; 381: 796–800Crossref | PubMed | Scopus (447)See all ReferencesWong et al. 1996). This result suggests that TR1 and TR2 receptors must couple to a still undefined signal transduction pathway, and that gustducin might either be coexpressed with a different class of receptor for bitter or sweet (see below) or play a different role than anticipated.The identification of only two taste receptors comes as a big surprise. Could TR1 and TR2 really accommodate specific detection of all sweet and bitter compounds? A direct answer to this question will require functional analysis of TR1 and TR2 activation. On one hand, the existence of very promiscuous taste receptors would fit well with the lack of discrimination observed between chemical stimuli within a given taste modality. However, the extreme heterogeneity in the chemical structures of tastants (carbohydrates, amino acids, proteins, inorganic salts, and a large variety of artificial sweeteners can elicit the perception of sweet) and the absence of cross-desensitization between different tastants support the existence of additional taste receptors (Linderman 1996xLinderman, B. Physiol. Rev. 1996; 76: 718–766PubMedSee all ReferencesLinderman 1996).TR1 and TR2 receptor sequences share 40% sequence identity with each other and show a more distant similarity with those of the mammalian pheromone and metabotropic neurotransmitter receptors. Extensive search by Hoon et al. for TR1 and TR2 homologs in the tongue has been unsuccessful, hinting at the existence of several highly divergent, possibly unrelated gene families encoding taste receptors. The existence of multiple families of G protein–coupled receptors carrying taste detection would be quite reminiscent of the extreme diversity found among chemosensory and olfactory receptors in vertebrates and C. elegans (2xBuck, L. and Axel, R. Cell. 1991; 65: 175–187Abstract | Full Text PDF | PubMed | Scopus (2085)See all References, 3xDulac, C. and Axel, R. Cell. 1995; 83: 195–206Abstract | Full Text PDF | PubMed | Scopus (691)See all References, 11xTroemel, E.R., Chou, J.H., Dwyer, N.D., Colbert, H.A., and Bargmann, C.I. Cell. 1995; 83: 207–218Abstract | Full Text PDF | PubMed | Scopus (439)See all References, 9xSengupta, P., Chou, J.H., and Bargmann, C.I. Cell. 1996; 84: 899–909Abstract | Full Text | Full Text PDF | PubMed | Scopus (317)See all References, 5xHerrada, G. and Dulac, C. Cell. 1997; 90: 763–773Abstract | Full Text | Full Text PDF | PubMed | Scopus (493)See all References, 8xMatsunami, H. and Buck, L.B. Cell. 1997; 90: 775–784Abstract | Full Text | Full Text PDF | PubMed | Scopus (484)See all References; Ryba and Trindelli, 1997), and would underline the necessity to accommodate specific recognition of structurally diverse ligands.What is the molecular organization of the taste sensory epithelium? In the vertebrate olfactory system, individual olfactory sensory neurons express only one olfactory receptor gene, and all sensory neurons expressing the same receptor establish synapses with a specific subpopulation of mitral cells in the olfactory bulb. The activation of different olfactory receptors thus elicits different patterns of mitral cell activation in the brain, providing a simple neuronal mechanism for discrimination between odorants (Buck 1996xBuck, L. Annu. Rev. Neurosci. 1996; 19: 517–544Crossref | PubMedSee all ReferencesBuck 1996). How many receptors does an individual taste cell express? Do individual sensory fibers establish synapses with taste receptor cells expressing a specific receptor, or do they integrate sensory stimuli from multiple subpopulations of taste neurons? Hoon et al. have shown that 20%–30% of taste receptor cells in taste buds of the fungiform and circumvallate papillae are, respectively, TR1 and TR2 positive. If more than two or three additional receptors for either sweet or bitter chemicals were to be found, it would probably imply that individual taste receptor cells express more than one taste receptor gene. Thus, in contrast to that of the vertebrate olfactory system, the molecular organization of the taste sensory system might not be able to afford discrimination between individual chemical stimuli. Is such discrimination achieved? If so, how? For the next few years, TR1 and TR2 are likely to provide precious tools to tackle the largely mysterious logic of taste sensory signaling. This is but a taste of things to come.Figure 1Schematic Organization of Taste Sensory Neurons The tongue epithelium displays regional preferences to sweet, bitter, sour, and salty compounds. TR2, the putative receptor for bitter tastants, is localized in the apical membrane of taste receptor cells, mostly, although not exclusively, in taste buds of circumvallate papillae in the back of the tongue that show preferential sensitivity to bitter. In contrast, TR1, the putative receptor for sweet, is mainly expressed in taste cells of fungiform papillae of the front of the tongue that show gustatory preference for sweet compounds.View Large Image | View Hi-Res Image | Download PowerPoint Slide