FRPR-1, a G protein-coupled receptor in the FMRFamide-related peptide receptor family, modulates larval development as a receptor candidate of the FMRFamide-like peptide FLP-1 in Caenorhabditis elegans.

FMRFamide-like peptides (FLPs) and their receptors, FMRFamide-related peptide receptors (FRPRs) are widely conserved in free-living and parasitic nematodes. Herein, we identified FRPR-1 as an FLP-1 receptor candidate involved in larval development and diapause in the model nematode Caenorhabditis elegans. Our molecular genetic study, supported by in silico research, revealed the following: (1) frpr-1 loss-of-function completely suppresses the promotion of larval diapause caused by flp-1 overexpression; (2) AlphaFold2 analysis revealed the binding of FLP-1 to FRPR-1; (3) FRPR-1 as well as FLP-1 modulates the production and secretion of the predominant insulin-like peptide DAF-28, which is produced in ASI neurons; and (4) the suppression of larval diapause by frpr-1 loss-of-function is completely suppressed by a daf-28 defect. Thus, FRPR-1 regulates larval development and diapause by modulating DAF-28 production and secretion. This study may provide new insights into the development of novel nematicides targeting parasitic nematodes using FRPR-1 inhibitors.