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

Nat Neurosci. 2003 Nov;6(11):1178-85. doi: 10.1038/nn1140. Epub 2003 Oct 12.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Behavior, Animal
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / classification
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Dose-Response Relationship, Drug
  • FMRFamide / metabolism*
  • Feeding Behavior / physiology*
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Ligands
  • Membrane Potentials
  • Microinjections
  • Microscopy, Confocal
  • Mutation
  • Neuropeptides / pharmacology
  • Oocytes
  • Patch-Clamp Techniques
  • Peptides / pharmacology
  • Pharyngeal Muscles / drug effects
  • Pharyngeal Muscles / physiology
  • Phenylalanine / genetics
  • Potassium Channels / metabolism
  • Potassium Channels, Inwardly Rectifying*
  • Receptors, Neuropeptide Y / classification
  • Receptors, Neuropeptide Y / genetics
  • Receptors, Neuropeptide Y / metabolism*
  • Sequence Homology, Amino Acid
  • Social Behavior*
  • Transformation, Genetic
  • Valine / genetics
  • Xenopus laevis


  • Caenorhabditis elegans Proteins
  • Flp-1 protein, C elegans
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Ligands
  • NPR-1 protein, C elegans
  • Neuropeptides
  • Peptides
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Neuropeptide Y
  • Phenylalanine
  • FMRFamide
  • Valine