Benelux Congress of Zoology edition:14 location:Amsterdam date:1-2 november 2007
Neuropeptides comprise a class of structural diverse messenger molecules that occur in the whole animal kingdom where they play many roles in the regulation of physiological processes and behaviour by binding to G protein-coupled receptors (GPCRs). Two important classes of neuropeptides in insects are CAPA peptides (orthologues of Drosophila melanogaster peptides encoded on the gene capability), which cause myotropic effects or (anti-)diuretic effects, and adipokinetic homones (AKH), which are involved in energy mobilisation during flight. A BLAST search of these insect CAPA and AKH receptors in the Caenorhabditis elegans genome revealed potential nematode orthologues for both of them. Both C. elegans receptor encoding genes were expressed in mammalian cells which were screened against synthetic C. elegans peptides and HPLC fractions of a C. elegans peptide extract in order to find the corresponding ligands. This way, the putative GPCRs were deorphanized by means of a reversed pharmacological approach. Not only do the CAPA and AKH receptors from insects show remarkable sequence resemblance with their counterparts in the nematode C. elegans, their activating peptide ligands also display similar motifs. Moreover, the insect and nematode AKH receptors are related to the mammalian gonadotropin realeasing hormone receptor. Taken all together, this points to co-evolution of neuropeptides and their receptors in arthropods and nematodes, as well as in mammals, at least at the structural level. Conservation of the physiological functions of these peptides and receptors, however, remains to be investigated.