Functional expression and characterization of the C. elegans G-protein-coupled FLP-2 Receptor (T19F4.1) in mammalian cells and yeast

Profound neuropeptide diversity characterizes the nematode nervous system, but it has proven challenging to match neuropeptide G protein-coupled receptors (GPCR) with their cognate ligands in heterologous systems. We have expressed the Caenorhabditis elegans GPCR encoded in the locus T19F4.1, previously matched with FMRFamide-like peptides encoded on the flp-2 precursor gene, in mammalian cells and in the yeast Saccharomyces cerevisiae. Pharmacological characterization revealed that the receptor is potently activated by flp-2 peptides in CHO cells (∼10 nM EC50) and in yeast (∼100 nM EC50), signaling through a Gqα pathway in each system. The yeast GPCR expression system provides a robust assay for screening for agonists of the flp-2 receptor and is the target of an ongoing high-throughput screening exercise.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Nematode neuropeptide G protein-coupled receptors are good targets for anthelmintic discovery. ► Neuropeptides encoded on the Caenorhabditis elegans flp-2 gene are bioactive in parasite assays. ► The receptor for flp-2 peptides has been functionally expressed in mammalian cells and yeast. ► The recombinant yeast expressing this receptor is the focus of an ongoing drug discovery effort.