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.
Rogers
Candida
C
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
Reale
Vincenzina
V
Kim
Kyuhyung
K
Chatwin
Heather
H
Li
Chris
C
Evans
Peter
P
de Bono
Mario
M
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019835:FMRFamide / Q000378:metabolism*; D005247:Feeding Behavior / Q000502:physiology*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D008024:Ligands; D008564:Membrane Potentials; D008845:Microinjections; D018613:Microscopy, Confocal; D009154:Mutation; D009479:Neuropeptides / Q000494:pharmacology; D009865:Oocytes; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D010609:Pharyngeal Muscles / Q000187:drug effects / Q000502:physiology; D010649:Phenylalanine / Q000235:genetics; D015221:Potassium Channels / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D017476:Receptors, Neuropeptide Y / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012919:Social Behavior; D014170:Transformation, Genetic; D014633:Valine / Q000235:genetics; D014982:Xenopus laevis
D029742:Caenorhabditis elegans Proteins; C114560:Flp-1 protein, C elegans; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D008024:Ligands; C468272:NPR-1 protein, C elegans; D009479:Neuropeptides; D010455:Peptides; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D017476:Receptors, Neuropeptide Y; D010649:Phenylalanine; D019835:FMRFamide; D014633:Valine