Drosophila taste receptors reveal combinatorial and cross-modality functions. Erica Freeman¹, Alice French², Zev Wisotsky³, Frédéric Marion-Poll^2,4, Anupama Dahanukar^1,3,5. 1) Bioengineering Graduate Program, University of California, Riverside, CA; 2) INRA, Physiologie de l'Insecte: Signalisation et Communication, Versailles, France; 3) Neuroscience Program, University of California, Riverside, CA; 4) AgroParisTech, Départment Sciences de la Vie et Santé, Paris Cedex 05, France; 5) Department of Entomology, University of California, Riverside, CA.

   Drosophila melanogaster use a highly diverse group of gustatory receptors (Gr) to taste the chemical world and determine the palatability of potential food sources. The 68 receptors of this family are expressed in complex combinatorial patterns in taste neurons. Of these, eight belong to a sub-family of putative sugar receptors, at least four of which have been directly linked to the detection of sweet compounds by genetic analysis. Here we use an ectopic expression system to identify that each sweet Gr protein serves as a determinant for recognition of unique but overlapping subsets of sweet tastants. Together with analysis of available Gr mutants, the ectopic response profiles suggest a model in which receptors act in combinations of two or more Gr subunits, each contributing to ligand recognition and specificity. Interestingly, we discover that sweet Grs are directly inhibited by bitter alkaloids, and individual Gr proteins display specificity for bitter antagonists. Recordings from Drosophila confirm that alkaloids can inhibit sugar responses of sweet taste neurons in a manner that is independent of their excitatory activity on bitter taste neurons. A comparison of sweet neuron responses in two species of mosquitoes, Anopheles gambiae and Aedes aegypti, suggests that such mechanisms of sweet receptor inhibition by bitter alkaloids may be evolutionarily conserved. Our results reveal combinatorial mechanisms for sweet and bitter ligand recognition by sweet taste receptors, and lay the foundation for further investigation of Gr function in Drosophila and other insects.