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.
Highlights
An estimated 1.5 billion people, comprising 24% of the world’s population, are infected with soil-transmitted helminthes [1]
FLP-1 neuropeptides in C. elegans which are supported by NIH RCMI (8G12MD007603) Strains from the Caenorhabitis Genetics Center, which is supported by the NIH Office of Research Infrastructure Programs (P40 OD010440)
We previously reported that the deletion of flp-1 caused numerous behavioral defects in C. elegans, including a reduced response to being touched on the nose, a reduced sensitivity to hyperosmolarity, locomotory defects, and an increased tendency to wander off a food source [22]. flp-1 mutants were found to have egg-laying defects [24], which were potentiated in the presence of serotonin [25]
Summary
An estimated 1.5 billion people, comprising 24% of the world’s population, are infected with soil-transmitted helminthes [1]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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