Neuropeptides represent a diverse and numerous class of signaling molecules in the nervous system, of which over 250 distinct sequences have been identified in the C. elegans genome so far. Through binding of G protein-coupled receptors (GPCRs), neuropeptides are thought to primarily transmit and modulate synaptic and endocrine functions. Therefore, they act as key players in the regulation of animal physiology including reproduction, locomotion, feeding and social behavior. Despite their clear role in neuronal signaling and behavior, neuropeptide functions and the underlying signaling pathways they govern are still not well understood. Identification of the receptors that bind neuropeptides should gain more insights into neuropeptidergic signaling. Over the years, our research group has successfully used expertise on GPCR deorphanization techniques to characterize several neuropeptide mediated signaling systems in C. elegans including gonadotropin-releasing hormone (GnRH), cholecystokinine (CCK) and pigment dispersing factor (PDF) signaling. We now report the characterization of a novel vasopressin/oxytocin-like signaling system in C. elegans. Vasopressin (VP) and oxytocin (OT) are structurally related neurohypophysial peptides, first identified in vertebrates and more recently in some parts of the invertebrate lineage. By means of bioinformatic search methods, we have identified homologous genes for a VP/OT receptor and peptide precursor in the C. elegans genome. Structural features of the VP/OT superfamily have been generally conserved in C. elegans and other nematode species, both on the receptor and neuropeptide precursor level. Despite the overall conservation, the VP/OT-like peptide in C. elegans differs from the classical nonapeptide structure found in most vertebrate and invertebrate VP/OT peptides. We have cloned the C. elegans VP/OT receptor and expressed this GPCR in Chinese hamster ovary (CHO) cells upon characterization. The C. elegans VP/OT receptor was activated by the C. elegans VP/OT-like peptide through a Gaq protein (EC50 = 20 nM), but not by other members of the VP/OT family (e.g. inotocin, octopressin). Ongoing research focuses on the functional characterization of VP/OT signaling in nematodes. Preliminary localization studies indicate that the C. elegans VP/OT receptor is expressed in body wall muscles of all larval and adult stages as well as in vulval muscles of adult hermaphrodites, supporting an evolutionary conserved role of VP/OT signaling in muscle contraction and reproduction.

Affiliation:
- Laboratory of Functional Genomics and Proteomics, K.U.Leuven, Naamsestraat 59, 3000 Leuven, Belgium