Abstract:
Genetic studies undertaken in the model organism Caenorhabditis elegans have demonstrated the importance
of neuropeptidergic signalling in nematode physiology. Disruption of this signalling may have
deleterious phenotypic consequences, including altered locomotion, feeding behaviour, and reproduction.
Neuropeptide G protein-coupled receptors (GPCRs) that transduce many of these signals therefore
represent cogent drug targets. Recently published genomic sequencing data for a number of parasitic
helminths of medical and veterinary importance has revealed the apparent conservation of a number of
neuropeptides, and neuropeptide receptors between parasitic and free-living species, raising the intriguing
possibility of developing broad-spectrum anthelmintic therapeutics. Here, we identify and clone a
neuropeptide receptor, NPR-4, from the human filarial nematode Brugia malayi and demonstrate its activation
in vitro, by FMRFamide-like peptides of the FLP-18 family, and intracellular signalling via G i
mediated pathways. These data represent the first example of deorphanisation of a neuropeptide GPCR
in any parasitic helminth species.
