FLP-1 neuropeptides modulate sensory and motor circuits in the nematode Caenorhabditis elegans.

Abstract

Parasitic nematodes infect over one quarter of the population worldwide, causing morbidity in over one billion people. Current anthelmintic drugs are beginning to lose effectiveness due to the presence of resistant strains. We are interested in the role of neuropeptides, which regulate behaviors in all organisms, as another possible target for anthelmintic drugs. FMRFamide-related peptides (FaRPs) are a family of neuropeptides that are conserved throughout the animal kingdom. In particular, nematodes contain the largest family of FaRPs identified thus far and many of these FaRPs are identical among different nematode species; FaRPs in nematodes are collectively referred to as FLPs (FMRFamide-like peptides). However, little is known about the function of these FLPs. We are using the non-parasitic nematode Caenorhabditis elegans as a model for examining FLPs in nematodes. C. elegans contains at least 31 flp genes that encode 72 potential FLPs. Among the flp genes, flp-1 is one of the few that is universally found in nematodes. FLP-1 neuropeptides were previously reported to be involved in sensory and motor functions. However, previous alleles of flp-1 also disrupted a neighboring gene, daf-10. To understand the phenotypes of flp-1, new alleles that specifically disrupt flp-1 were characterized. The previously reported locomotory and egg-laying defects were found to be due to loss of flp-1, while the osmolarity defect is due to loss of daf-10. In addition, loss of flp-1 and daf-10 both cause several phenotypes that increase in severity in the double mutants by disrupting different neurons in the neural circuits.