Opposing chemosensory functions of closely related gustatory receptors

Abstract

ABSTRACTMost animals have functionally distinct populations of taste cells, expressing receptors that are tuned to compounds of different valence. This organizational feature allows for discrimination between chemicals associated with specific taste modalities and facilitates differentiating between unadulterated foods and foods contaminated with toxic substances. In the fruit flyD. melanogaster, primary sensory neurons express taste receptors that are tuned to distinct groups of chemicals, thereby activating neural ensembles that elicit either feeding or avoidance behavior. Members of a family of ligand gated receptor channels, the Gustatory receptors (Grs), play a central role in these behaviors. In general, closely related, evolutionarily conserved Gr proteins are co-expressed in the same type of taste neurons, tuned to chemically related compounds, and therefore triggering the same behavioral response. Here, we report that members of the Gr28 subfamily are expressed in largely non-overlapping sets of taste neurons inDrosophilalarvae, detect chemicals of different valence and trigger opposing feeding behaviors. We determined the intrinsic properties ofGr28neurons by expressing the mammalian Vanilloid Receptor (VR1), which is activated by capsaicin, a chemical to which wildtypeDrosophilalarvae do not respond. When VR1 is expressed inGr28aneurons, larvae become attracted to capsaicin, consistent with reports showing thatGr28aitself encodes a receptor for nutritious RNA. In contrast, expression of VR1 in two pairs ofGr28b.cneurons triggers avoidance to capsaicin. Moreover, neuronal inactivation experiments show that theGr28b.cneurons are necessary for avoidance of several bitter compounds. Lastly, behavioral experiments ofGr28deficient larvae and live Ca2+imaging studies ofGr28b.cneurons revealed that denatonium benzoate, a synthetic bitter compound that shares structural similarities with natural bitter chemicals, is a ligand for a receptor complex containing a Gr28b.c or Gr28b.a subunit. Thus, theGr28proteins, which have been evolutionarily conserved over 260 million years in insects, represent the first taste receptor subfamily in which specific members mediate behavior with opposite valence.