EpOME functionally antagonises prostaglandin signalling in Spodoptera exigua via a specific GPCR conserved across metazoans.
5 affiliations
- 1School of Life Science & Engineering, Gyeongkuk National University, Andong, Korea.
- 2Division of Biomedical Metrology, Korea Research Institute of Standards and Science, Daejeon, Korea.
- 3Industry Academy Cooperation Foundation, Gyeongkuk National University, Andong, Korea.
- 4Department of Pharmacy, Section for Pharmaceutical Chemistry, University of Oslo, Oslo, Norway.
- 5School of Life Science & Engineering, Gyeongkuk National University, Andong, Korea. [email protected].
Abstract
The eicosanoid PGE₂ upregulates intracellular Ca²⁺/cAMP levels and induces a cellular immune response, whereas EpOME inhibits PGE₂ activity in insects. However, the molecular interactions between the two antagonistic ligands remain largely unexplored. Here we identify nine homologs of vertebrate C18-oxylipin-associating GPCRs among the GPCRs of Spodoptera exigua (SeGPCRs). Functional homology is validated through RNA interference screening, followed by heterologous expressions in both directions between insect and human cell lines. A deletion mutant of SeGPCR48, generated via CRISPR/Cas9, loses responsiveness to EpOME, which is confirmed functionally and by differential gene expression analysis following RNA-seq. In silico binding assay indicate high binding affinity of EpOME to SeGPCR48, which is supported by experimental follow-up, involving ligand-binding functional assays and point mutagenesis of two residues in the binding pocket. In congruence with the in vitro experiments, the EpOME-SeGPCR48 ligand-receptor pair showed marked inhibitory activity against PGE₂-mediated immunity. Collectively, this study identifies an insect EpOME receptor within an orphan GPCR subfamily that is phylogenetically conserved across metazoans.
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BibTeX
@article{shahmohammadi2026epome,
title = {{EpOME functionally antagonises prostaglandin signalling in Spodoptera exigua via a specific GPCR conserved across metazoans.}},
author = {Niayesh Shahmohammadi and Falguni Khan and Haneol Jang and Il-Hwan Kim and Donghee Lee and Joseph Wallen and Hyeok Jin Choi and Jin Boo Jeong and Anders Vik and Yonggyun Kim},
journal = {Nature communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77858-6},
url = {https://europepmc.org/article/MED/42907432},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - EpOME functionally antagonises prostaglandin signalling in Spodoptera exigua via a specific GPCR conserved across metazoans.
AU - Niayesh Shahmohammadi
AU - Falguni Khan
AU - Haneol Jang
AU - Il-Hwan Kim
AU - Donghee Lee
AU - Joseph Wallen
AU - Hyeok Jin Choi
AU - Jin Boo Jeong
AU - Anders Vik
AU - Yonggyun Kim
PY - 2026
DA - 2026/09/22
JO - Nature communications
DO - 10.1038/s41467-026-77858-6
UR - https://europepmc.org/article/MED/42907432
AB - The eicosanoid PGE₂ upregulates intracellular Ca²⁺/cAMP levels and induces a cellular immune response, whereas EpOME inhibits PGE₂ activity in insects. However, the molecular interactions between the two antagonistic ligands remain largely unexplored. Here we identify nine homologs of vertebrate C18-oxylipin-associating GPCRs among the GPCRs of Spodoptera exigua (SeGPCRs). Functional homology is validated through RNA interference screening, followed by heterologous expressions in both directions between insect and human cell lines. A deletion mutant of SeGPCR48, generated via CRISPR/Cas9, loses responsiveness to EpOME, which is confirmed functionally and by differential gene expression analysis following RNA-seq. In silico binding assay indicate high binding affinity of EpOME to SeGPCR48, which is supported by experimental follow-up, involving ligand-binding functional assays and point mutagenesis of two residues in the binding pocket. In congruence with the in vitro experiments, the EpOME-SeGPCR48 ligand-receptor pair showed marked inhibitory activity against PGE₂-mediated immunity. Collectively, this study identifies an insect EpOME receptor within an orphan GPCR subfamily that is phylogenetically conserved across metazoans.
SN - 2041-1723
ER -