Une Risako, Uegaki Riko, Maega Sho, Ono Masahiro, Bito Tomohiro, Iwasaki Takashi, Shiraishi Akira, Satake Honoo, Kawano Tsuyoshi
Department of Agricultural Science, Graduate School of Sustainability Science, Tottori University, 680-8553 Tottori, Japan.
Department of Bioresources Science, The United Graduate School of Agriculture, Tottori University, 680-8553 Tottori, Japan.
Biosci Biotechnol Biochem. 2025 Mar 24;89(4):586-593. doi: 10.1093/bbb/zbaf004.
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.
类FMRF酰胺肽（FLPs）及其受体，即FMRF酰胺相关肽受体（FRPRs），在自由生活和寄生的线虫中广泛存在。在此，我们鉴定出FRPR-1是模式线虫秀丽隐杆线虫中参与幼虫发育和滞育的FLP-1受体候选物。我们的分子遗传学研究，在计算机模拟研究的支持下，揭示了以下内容：（1）frpr-1功能缺失完全抑制了flp-1过表达引起的幼虫滞育促进作用；（2）AlphaFold2分析揭示了FLP-1与FRPR-1的结合；（3）FRPR-1以及FLP-1调节主要在ASI神经元中产生的胰岛素样肽DAF-28的产生和分泌；（4）frpr-1功能缺失对幼虫滞育的抑制作用被daf-28缺陷完全抑制。因此，FRPR-1通过调节DAF-28的产生和分泌来调节幼虫发育和滞育。这项研究可能为使用FRPR-1抑制剂开发针对寄生线虫的新型杀线虫剂提供新的见解。
