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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Action Potentials / drug effects
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Action Potentials / physiology
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Animals
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Behavior, Animal
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Caenorhabditis elegans / physiology*
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Caenorhabditis elegans Proteins / classification
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Dose-Response Relationship, Drug
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FMRFamide / metabolism*
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Feeding Behavior / physiology*
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G Protein-Coupled Inwardly-Rectifying Potassium Channels
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Ligands
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Membrane Potentials
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Microinjections
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Microscopy, Confocal
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Mutation
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Neuropeptides / pharmacology
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Oocytes
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Patch-Clamp Techniques
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Peptides / pharmacology
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Pharyngeal Muscles / drug effects
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Pharyngeal Muscles / physiology
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Phenylalanine / genetics
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Potassium Channels / metabolism
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Potassium Channels, Inwardly Rectifying*
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Receptors, Neuropeptide Y / classification
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Receptors, Neuropeptide Y / genetics
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Receptors, Neuropeptide Y / metabolism*
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Sequence Homology, Amino Acid
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Social Behavior*
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Transformation, Genetic
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Valine / genetics
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Xenopus laevis
Substances
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Caenorhabditis elegans Proteins
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Flp-1 protein, C elegans
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G Protein-Coupled Inwardly-Rectifying Potassium Channels
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Ligands
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NPR-1 protein, C elegans
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Neuropeptides
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Peptides
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Potassium Channels
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Potassium Channels, Inwardly Rectifying
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Receptors, Neuropeptide Y
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Phenylalanine
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FMRFamide
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Valine