GPCRS and TRPA channels: Putative targets for insect repellents.

摘要

Many insects such as mosquitoes cause life-threatening diseases such as malaria, yellow fever and West Nile virus. Malaria alone infects 500 million people annually and causes 1-3 million death per year. Volatile insect repellents, which are detected through the sense of smell, have long been used to protect humans against insect pests. Antifeedants are non-volatile aversive compounds that are detected through the sense of taste and prevent insects from feeding on plants. The molecular targets for naturally occurring insect repellents were unknown. Here, we found that the Drosophila TRPA1 channel functioned in sensing the insect repellent citronellal. The response to citronellal relied on a G protein (Gq)/phospholipase C (PLC) signaling cascade. In contrast to fly TRPA1, Anopheles gambiae TRPA1 was directly and potently activated by citronellal. Another TRPA channel Painless (Pain) was required for sensing the insect repellents geraniol and camphor via a Gq/PLC signaling cascade. Aedes aegypti Pain was directly activated by A1TC, the pungent ingredient of wasabi. Our study identified mosquito TRPA channels as a potential target for developing improved repellents. We also found that TRPA1 was expressed in gustatory receptor neurons (GRNs) that responded to aversive compounds. TRPA1 was required in a subset of avoidance GRNs for the behavioral and electrophysiological responses to aristolochic acid, but not for the responses to most bitter compounds. TRPA1 did not appear to be activated directly by aristolochic acid, but was coupled to a PLC signaling cascade. Given that mammalian TRPA1 is required for responding to noxious chemicals, our analysis underscore the evolutionarily conserved role for TRPA1 channels in chemical avoidance. Most recently, we found that a rhodopsin initiated the Gq/PLC/TRPA signaling cascades that functioned in the avoidance of citronellal. Thus, a classical G-protein coupled receptor participates in chemosensation. In conclusion, our data demonstrate that TRPA channels and rhodopsin are crucial for multiple sensory inputs, including odorants and tastants.