Inhibition of Caenorhabditis elegans social feeding by FMRFamide-related peptide activation of NPR-1.

Social and solitary feeding in natural Caenorhabditis elegans isolates are associated with two alleles of the orphan G-protein-coupled receptor (GPCR) NPR-1: social feeders contain NPR-1 215F, whereas solitary feeders contain NPR-1 215V. Here we identify FMRFamide-related neuropeptides (FaRPs) encoded by the flp-18 and flp-21 genes as NPR-1 ligands and show ...
that these peptides can differentially activate the NPR-1 215F and NPR-1 215V receptors. Multicopy overexpression of flp-21 transformed wild social animals into solitary feeders. Conversely, a flp-21 deletion partially phenocopied the npr-1(null) phenotype, which is consistent with NPR-1 activation by FLP-21 in vivo but also implicates other ligands for NPR-1. Phylogenetic studies indicate that the dominant npr-1 215V allele likely arose from an ancestral npr-1 215F gene in C. elegans. Our data suggest a model in which solitary feeding evolved in an ancestral social strain of C. elegans by a gain-of-function mutation that modified the response of NPR-1 to FLP-18 and FLP-21 ligands.
Mesh Terms:
Action Potentials, Animals, Behavior, Animal, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Dose-Response Relationship, Drug, FMRFamide, Feeding Behavior, G Protein-Coupled Inwardly-Rectifying Potassium Channels, Ligands, Membrane Potentials, Microinjections, Microscopy, Confocal, Mutation, Neuropeptides, Oocytes, Patch-Clamp Techniques, Peptides, Pharyngeal Muscles, Phenylalanine, Potassium Channels, Potassium Channels, Inwardly Rectifying, Receptors, Neuropeptide Y, Sequence Homology, Amino Acid, Social Behavior, Transformation, Genetic, Valine, Xenopus laevis
Nat. Neurosci.
Date: Nov. 01, 2003
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