Ocular Albinism Type 1 Regulates Deltamethrin Tolerance in Lymantria dispar and Drosophila melanogaster

The ocular albinism type 1 (OA1), a pigment cell-specific integral membrane glycoprotein, is a member of the G-protein-coupled receptor (GPCR) superfamily that binds to heterotrimeric G proteins in mammalian cells. We aimed to characterize the physiological functions an insect OA1 from Lymantria dispar (LdOA1) employs in the regulation of insecticide tolerance. In the present study, we investigated the roles of LdOA1 in response to deltamethrin exposure in both L. dispar and Drosophila melanogaster. LdOA1 was expressed at the lowest level during the 4(th) instar stage, while LdOA1 was significantly upregulated in the 5(th) instar and male stages. Knockdown of LdOA1 by injecting dsRNA of LdOA1 into gypsy moth larvae caused a 4.80-fold higher mortality than in control larvae microinjected with dsRNA of GFP under deltamethrin stress. Nine out of 11 L. dispar CYP genes were significantly downregulated under deltamethrin stress in LdOA1 silenced larvae as compared to control larvae. Moreover, the LdOA1 gene was successfully overexpressed in D. melanogaster using transgenic technique. The deltamethrin contact assay showed that the LdOA1 overexpression in flies significantly enhanced the tolerance to deltamethrin compared to the control flies. Furthermore, the downstream Drosophila CYP genes were upregulated in the LdOA1 overexpression flies, suggesting LdOA1 may play a master switch role in P450-mediated metabolic detoxification. This study is the first report of an insect OA1 gene regulating insecticide tolerance and potentially playing a role in the regulation of downstream cytochrome P450 expression. These results contribute to the future development of novel insecticides targeting insect GPCRs.