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PMID:14555955

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Citation

Rogers, C, Reale, V, Kim, K, Chatwin, H, Li, C, Evans, P and de Bono, M (2003) Inhibition of Caenorhabditis elegans social feeding by FMRFamide-related peptide activation of NPR-1. Nat. Neurosci. 6:1178-85

Abstract

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.

Links

PubMed Online version:10.1038/nn1140

Keywords

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

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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