Social and solitary feeding behavior in wild isolates of C. elegans are associated with two isoforms of the putative neuropeptide receptor NPR-11. Wild isolates that feed in groups encode NPR-1 215F, while wild isolates that feed alone encode NPR-1 215V. Three other nematode species, C. briggsae, C. remanei and CB5161, all encode NPR-1 215F, suggesting that NPR-1 215V, which is genetically dominant over NPR-1 215F, arose in C. elegans by a gain-of-function change. To explore how the two NPR-1 receptor isoforms differ in their biological activity we identified ligands for NPR-1. We screened Xenopus oocytes expressing the NPR-1 215F receptor with 33 synthetic neuropeptides predicted from the C. elegans genome2. A FMRFamide related peptide encoded by the
flp-21 gene, GLGPRPLRFamide, but not other tested ligands, activated NPR-1 215F at nanomolar concentrations. To elucidate how the NPR-1 215F and NPR-1 215V forms of the receptor differ, we compared their signalling properties in Xenopus oocytes. We find that the genetically dominant NPR-1 215V form of the receptor is 50% activated at a 10-fold lower concentration of FLP-21 than NPR-1 215F. Preliminary results suggest that over-expression of
flp-21 induces solitary feeding in wild social C.elegans strains, but not in
npr-1(null) mutants, suggesting that FLP-21 is the endogenous ligand for this receptor. The role of FLP-21 as a neurotransmitter in the regulation of social feeding behaviour will be further investigated using electrophysiological techniques.