Appropriate food choices are critical for the acquisition of nutrients for growth, energy expenditure and reproduction. Taste perception is the primary sensory modality for the identification of nutritious compounds, such as carbohydrates, proteins, salts and fats, as well as harmful and toxic compounds, such as alkaloids, terpenoids and phenols, chemicals perceived as bitter by humans. Drosophila has served as an important model system to dissect the molecular basis of many sensory processes, including taste perception. The genomic/genetic resources are excellent and researchers have an impressive array of molecular-genetic, electrophysiological and imaging tools at their disposal, while the system is also amenable to elegant behavioral assays. Even though mammals and insects express evolutionarily distinct sets of taste receptors, the overall organization of taste sensory systems and especially the logic of taste coding are similar. Thus, the fly provides an opportunity to uncover basic mechanisms of taste perception, as well as organizing principle of their neural circuits. The Drosophila genome harbors 68 Gustatory receptor (Gr) genes, a subfamily of eight is thought to encode all putative sugar receptors. However, a model has emerged over the last few years that posits that only two heterodimeric sugar receptors (Gr5a/Gr64a and Gr5a/Gr64f) mediate most or all of sweet taste. We have tested this hypothesis using specific knock-in/expression alleles, as well as `sugar blind' Drosophila strains. These studies let us conclude that two major premises of this model need revision: First, Gr64a is not a major mediator of sweet taste and second, all sugar Gr proteins participate as units of functional sweet taste receptors. Moreover, while sugar receptors do function as multimeric complexes, Gr composition for most taste receptors is unknown. This gap in knowledge will be systematically filled with a methodical rescue strategy. We will also build on our recent discovery that sweet taste cells in the fly are not exclusively tuned to sugars, but also respond t fatty acids, another important nutritional component for almost all animals, including fruit flies.In preliminary studies, we have identified the first receptor gene necessary for fatty acid taste, a member of the Ionotropic receptor gene family. We will investigate the role of other members if this gene family by studying both their expression, as well as their function in fatty acid taste. Lastly, we discovered an entirely new taste modality, tuned to carboxylic acids but not acid in general. Carboxylic acids are generic components present in many fruits. We will determine the response profile of taste cells that specifically respond to these food components, and possibly to amino acids, and search for the receptors that recognize these compounds using a targeted candidate gene approach.
This research is relevant to public health because it will lead to the discovery of novel mechanisms that are critical during feeding. Using Drosophila as a powerful model system, our research has identified receptors that mediate distinct appetitive taste behaviors. One group of receptors is necessary for the detection of sweet chemicals in food, specifically sugars, which are a critical energy resource for most animals. A second group of receptors is necessary for the detection of other nutritious compounds, fatty acids. How such food chemicals are recognized is of general interest, as they are intimately coupled to feeding behavior. Studies in the fruit fly model system are also relevant because they have the potential to uncover basic mechanisms in less time, with less money and under more controlled conditions than when using mammalian systems. They are especially relevant in the discovery phase of poorly understood processes shared between animals and humans, such as the taste and consumption of fatty acid containing foods.
|Chen, Yan; Amrein, Hubert (2017) Ionotropic Receptors Mediate Drosophila Oviposition Preference through Sour Gustatory Receptor Neurons. Curr Biol 27:2741-2750.e4|
|Fujii, Shinsuke; Yavuz, Ahmet; Slone, Jesse et al. (2015) Drosophila sugar receptors in sweet taste perception, olfaction, and internal nutrient sensing. Curr Biol 25:621-627|
|Miyamoto, Tetsuya; Amrein, Hubert (2014) Diverse roles for the Drosophila fructose sensor Gr43a. Fly (Austin) 8:19-25|
|Yavuz, Ahmet; Jagge, Christopher; Slone, Jesse et al. (2014) A genetic tool kit for cellular and behavioral analyses of insect sugar receptors. Fly (Austin) 8:189-96|
|Chen, Yan; Amrein, Hubert (2014) Enhancing perception of contaminated food through acid-mediated modulation of taste neuron responses. Curr Biol 24:1969-77|
|Miyamoto, Tetsuya; Wright, Geraldine; Amrein, Hubert (2013) Nutrient sensors. Curr Biol 23:R369-73|
|Miyamoto, Tetsuya; Chen, Yan; Slone, Jesse et al. (2013) Identification of a Drosophila glucose receptor using Ca2+ imaging of single chemosensory neurons. PLoS One 8:e56304|
|Mishra, Dushyant; Miyamoto, Tetsuya; Rezenom, Yohannes H et al. (2013) The molecular basis of sugar sensing in Drosophila larvae. Curr Biol 23:1466-71|
|Miyamoto, Tetsuya; Slone, Jesse; Song, Xiangyu et al. (2012) A fructose receptor functions as a nutrient sensor in the Drosophila brain. Cell 151:1113-25|
|Wang, Liming; Han, Xiaoqing; Mehren, Jennifer et al. (2011) Hierarchical chemosensory regulation of male-male social interactions in Drosophila. Nat Neurosci 14:757-62|
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