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.
| Original language | English |
|---|---|
| Pages (from-to) | 1178-1185 |
| Number of pages | 8 |
| Journal | Nature Neuroscience |
| Volume | 6 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2003 |
Bibliographical note
Funding Information:We are grateful to R. Plasterk for allowing us to screen his C. elegans deletion library; Y. Kohara for flp-21 cDNAs; S. Baird, H. Kagawa, B. Fixsen, W. Sudhaus, A. Fodor, V. Ambros and W. Wood for wild isolates of C. briggsae and C. remanei and the Caenorhabditis Genetics Center for strains used in this work. We thank S. Baird, N. Tremain, G. Robinson and M. Sokolowski for comments on the manuscript and C. Bargmann, H. Baylis, C. Ferguson and B. Olofsson for discussion. This work was supported by the Medical Research Council (M.d.B.), the Biotechnology and Biological Sciences Research Council (P.E.) and grants from the National Science Foundation and National Institutes of Health (C.L.).