Gustatory receptor 22e is essential for sensing chloroquine and strychnine in Drosophila melanogaster

•Chloroquine is a potent anti-feedant at the range of 0.1-10 mM.•GR22e and GR33a are required for chloroquine avoidance behavior.•GR22e is also required for strychnine sensation.•GR22e is essential for recapitulating a chloroquine receptor as well as a strychnine receptor.

Chloroquine, an amino quinolone derivative commonly used as an anti-malarial drug, is known to impart an unpleasant taste. Little research has been done to study chloroquine taste in insects, therefore, we examined both the deterrant properties and mechanisms underlying chloroquine perception in fruit flies. We identified the antifeedant effect of chloroquine by screening 21 gustatory receptor (Grs) mutants through behavioral feeding assays and electrophysiology experiments. We discovered that two molecular sensors, GR22e and GR33a, act as chloroquine receptors, and found that chloroquine-mediated activation of GRNs occurs through S-type sensilla. At the same time, we successfully recapitulated the chloroquine receptor by expressing GR22e in ectopic gustatory receptor neurons. We also found that GR22e forms a part of the strychnine receptor. We suggest that the Drosophila strychnine receptor might have a very complex structure since five different GRs are required for strychnine-induced action potentials.

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