G Protein-Coupled Receptors as Target Sites for Insecticide Discovery

Abstract

G protein-coupled receptors (GPCR) are proteins that contain seven-transmembrane domains and sense external signals and transducer these signals by activating intercellular pathways. GPCR family is considered as the largest integrate membrane receptor family and GPCRs are present in almost all the eukaryotes tested. About 1–2% of all genes in an insect genome code for GPCRs. GPCRs do not share high overall sequence homology. Whole genome sequencing identified about 200 GPCRs in Drosophila melanogaster and 276 GPCRs in Anopheles gambiae. The biological function studies are mostly focused on neurohormone (biogenic amine, neuropeptide and protein hormone) GPCRs. Diverse functions of insect GPCRs in feeding behavior, locomotion activity, metabolism, circadian rhythm, development and reproduction have been characterized in the past few years. Although, more than 40% of the pharmaceutical drugs that are currently in the market target human GPCRs, there is not a single insecticide that target GPCR. We will review recent literature on ligand activated GPCRs identified from insects, in regards to their classification and functions, and discuss possible GPCR targets and screening assays to identify insecticides that target GPCRs.