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

Nature Neuroscience volume 6, pages 11781185 (2003) | Download Citation



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.

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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.).

Author information

Author notes

    • Candida Rogers
    •  & Vincenzina Reale

    These authors contributed equally to this work.


  1. MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.

    • Candida Rogers
    •  & Mario de Bono
  2. The Signalling Programme, The Babraham Institute, Cambridge CB2 4AT, UK.

    • Vincenzina Reale
    • , Heather Chatwin
    •  & Peter Evans
  3. Department of Biology, Boston University, 5 Cummington Street, Boston, Massachusetts 02215, USA.

    • Kyuhyung Kim
    •  & Chris Li


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The authors declare no competing financial interests.

Corresponding author

Correspondence to Mario de Bono.

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  1. 1.

    Supplementary Fig. 1.

    FaRPs encoded by flp-18 and flp-21 activate NPR-1. Membrane currents from Xenopus oocytes injected with cRNAs for GIRK 1, GIRK 2 and NPR-1 isoforms. Trace (a) is from an oocyte injected with NPR-1 215F cRNA, whereas in trace (b) the oocyte was injected with NPR-1 215V cRNA. The oocytes were clamped at -80 mV and the currents monitored before and after the application of a high K+ saline (open bars), during which time the peptide (1 μM) was also applied (solid bars). FLP-21 refers to the peptide GLGPRPLRFamide, whereas FLP-18 refers to the peptide EMPGVLRFamide. Both peptides activated GIRK currents in oocytes expressing the NPR-1 215V receptor, but the currents induced by FLP-21 are three times larger than those induced by FLP-18. In contrast, only FLP-21 activated GIRK currents in oocytes expressing the NPR-1 215F receptor. The two traces shown in each panel are from the same oocyte, with a gap of 400 s between each trace.

  2. 2.

    Supplementary Fig. 2.

    Representative intracellular recordings from C. elegans pharyngeal muscle showing the effects of FLP-18 and FLP-21 peptides on action potential frequency in animals expressing npr-1 transgenes under the control of the heat-shock promoter. Both the FLP-21 (a and c) and the FLP-18 EMPGVLRFamide (b and d) peptides induced a larger inhibition of action potential frequency in heat-shocked (+HS) animals expressing NPR-1 compared to non-heat-shocked controls (-HS). In all examples peptides were applied at a concentration of 10-10 M for 1 minute, as indicated by the horizontal bar. The NPR-1 receptor isoform tested is indicated above each panel. 500 nM 5HT was included in the perfusate to give a background firing rate against which to measure inhibition.

  3. 3.

    Supplementary Methods

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    Supplementary Table 1

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