Detection of energy rich nutrients and potentially toxic compounds is crucial for the regulation of food choices. In Drosophila, sweet and bitter tastants are detected by members of a highly diverse family of 68 Gustatory receptors (Grs). Eight of these receptors are expressed in sweet taste neurons and are part of an evolutionarily conserved clade. In a previous study, we developed an in vivo functional expression system to individually express these receptors in a unique olfactory neuron that senses carbon dioxide. This neuron is unique because it expresses gustatory receptors, Gr63a and Gr21a, which detect carbon dioxide but do not respond to any known tastants. By expressing sweet taste receptors individually in this olfactory neuron, we found that each receptor responds to unique but overlapping subsets of sweet tastants. We also tested Gr43a, an internal fructose receptor, and its mosquito ortholog AgGr25, and discovered that both receptors respond to fructose as well as other sugars. Thus, all sweet receptors are directly involved in the detection of sweet compounds.
Drosophila have been shown to detect aversive compounds via two different cellular mechanisms – activation of deterrent neurons and inhibition of appetitive neurons. Recent studies have found that an odorant binding protein (Obp49a) is required for bitter tastant inhibition of sweet taste neurons. From a systematic analysis of the dynamics of sweet neuron inhibition, we found that sensitivity to bitter tastants is reduced but not abolished in Obp49a mutants, suggesting that other mechanisms are involved. Moreover, bitter tastants did not evoke the same degree of inhibition when combined with different sugar agonists, raising the possibility of receptor specific antagonist effects. We therefore investigated whether sweet taste receptors were directly inhibited by bitter tastants using the ectopic expression system. We tested seven receptors of the sweet clade individually against a panel of 21 bitter compounds at different concentrations and found that sweet Grs could be directly inhibited by bitter tastants in a dose dependent manner. Moreover, sweet Grs have different sensitivity to different bitter tastants, as well as unique inhibitory response profiles. Interestingly, this property is a distinguishing feature of the sweet Gr clade – neither Gr43a nor the Gr21a/Gr63a receptors are inhibited by bitter tastants. Thus, sweet Grs appear to have evolved to sense both appetitive and aversive compounds.