G-Protein Coupled Receptors as Emerging Molecular Targets for Next-Generation Insect Pest Management
Keywords:
GPCRs, Neuropeptide receptors, RNA interference, CRISPR/Cas9, Physiological effects, Novel pest management, Signalling pathwayAbstract
Traditional chemical insecticides have been used for crop protection for year’s exhibit significant drawbacks. Pests may develop resistance to insecticides and the chemicals remain in the soil and water for long time. Furthermore, insecticides kill insects that are beneficial, such as bees and wasps. Scientists now explore more targeted approaches, focusing on the interference with G protein-coupled receptors (GPCRs), which are "molecular switches" within the insects controlling development, feeding, mating and behaviours. Due to the significance of these switches, targeting them is a promising way of eliminating pests without damaging effects on other organisms and the environment caused by traditional chemical insecticides. This article examines functioning of these receptors, including those involved in hormonal and neuropeptide signalling. Moreover, it describes recent methods developed for targeting GPCRs in insects, including RNA interference, CRISPR/Cas9-based genetic modification, computer-assisted drug design and virtual screening of molecules. While there are some obstacles in the development of such insecticides due to the limited knowledge about the receptors and difficulties in delivery of drugs to pests, rapid progress in genetics and computational biology contributes to the development of safer and smarter insecticides.
References
Altstein, M., & Nässel, D. R. (2010). Neuropeptide signaling in insects. In Advances in experimental medicine and biology (Vol. 692, pp. 155-165). Springer.
Bai, H., Zhu, F., Shah, K., & Palli, S. R. (2011). Large-scale RNAi screen of G protein-coupled receptors involved in larval growth, molting and metamorphosis in the red flour beetle. BMC Genomics, 12, 388.
Bendena, W. G. (2010). Neuropeptide physiology in insects. In Neuropeptide systems as targets for parasite and pest control (pp. 166-191).
Caers, J., Verlinden, H., Zels, S., Vandersmissen, H. P., Vuerinckx, K., & Schoofs, L. (2012). More than two decades of research on insect neuropeptide GPCRs: An overview. Frontiers in Endocrinology, 3, 151.
Fan, Y., Sun, P., Wang, Y., He, X., Deng, X., Chen, X., Zhang, G., Chen, X., & Zhou, N. (2010). The G protein-coupled receptors in the silkworm, Bombyx mori. Insect Biochemistry and Molecular Biology, 40(8), 581-591.
Hauser, F., Cazzamali, G., Williamson, M., Blenau, W., & Grimmelikhuijzen, C. J. (2006). A review of neurohormone GPCRs present in the fruitfly Drosophila melanogaster and the honey bee Apis mellifera. Progress in Neurobiology, 80(1), 1-19.
Hauser, F., Neupert, S., Williamson, M., Predel, R., Tanaka, Y., & Grimmelikhuijzen, C. J. (2010). Genomics and peptidomics of neuropeptides and protein hormones present in the parasitic wasp Nasonia vitripennis. Journal of Proteome Research, 9(10), 5296-5310.
Keyes-Scott, N. I., Swade, K. R., Allen, L. R., & Vogel, K. J. (2023). RNAi-mediated knockdown of two orphan G protein-coupled receptors reduces fecundity in the yellow fever mosquito Aedes aegypti. Frontiers in Insect Science, 3, 1197945.
Konopińska, N., Chowański, S., Lubawy, J., Marciniak, P., Walkowiak-Nowicka, K., Smagghe, G., & Urbański, A. (2025). Insect neuropeptides as agents for pest control: Potential and challenges. Biological Research, 59(1), 6.
Liu, N., Li, T., Wang, Y., & Liu, S. (2021a). G-protein coupled receptors (GPCRs) in insects-A potential target for new insecticide development. Molecules, 26(10), 2993.
Liu, N., Wang, Y., Li, T., & Feng, X. (2021b). G-protein coupled receptors (GPCRs): Signaling pathways, characterization, and functions in insect physiology and toxicology. International Journal of Molecular Sciences, 22(10), 5260.
Meeusen, T., Mertens, I., Clynen, E., Baggerman, G., Nichols, R., Nachman, R. J., & Schoofs, L. (2002). Identification in Drosophila melanogaster of the invertebrate G protein-coupled FMRFamide receptor. Proceedings of the National Academy of Sciences, 99(24), 15363-15368.
Nässel, D. R., & Wegener, C. (2011). A comparative review of short and long neuropeptide F signaling in invertebrates: Any similarities to vertebrate neuropeptide Y signaling? Peptides, 32(6), 1335-1355.
Nässel, D. R., & Zandawala, M. (2022). Endocrine cybernetics: Neuropeptides as molecular switches in behavioural decisions. Open Biology, 12(7), 220174.
Smagghe, G., & Swevers, L. (2012). Cell-based screening systems for insecticides. In Advanced technologies for managing insect pests (pp. 107-134).
Tanaka, Y. (2026). Comprehensive analysis of insect peptide hormones/neuropeptides by next-generation sequencing. In Insect peptide hormones and neuropeptides (pp. 75-96). Springer Nature Singapore.
Verlinden, H., Badisco, L., Marchal, E., Van Wielendaele, P., & Vanden Broeck, J. (2009). Endocrinology of reproduction and phase transition in locusts. General and Comparative Endocrinology, 162(1), 79-92.
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Copyright (c) 2026 S. Mohamed Ashick, Thandava Moorthy V, T. Pragadeeshwaran
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