Beets, Isabel et al. (2011) International Worm Meeting "Characterization of an evolutionary conserved vasopressin/oxytocin-like signaling system in C. elegans."

Temmerman, Liesbet, Schoofs, Liliane, Meelkop, Ellen, Beets, Isabel, Janssen, Tom, Lindemans, Marleen

[International Worm Meeting, 2011]

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.

J J Remy (2002) European Worm Meeting "Olfactive learning and memory in nematodes"

J J Remy

[European Worm Meeting, 2002]

We already suggested that olfactory imprinting (or odor memory) could exist in nematodes (Remy J.J., EWM 2000). Further experiments confirmed now that adults worms can be sensitized to odorant molecules that were present during a short period of their early development. For a number of C. elegans strains (N2, TR403, CB4705), as for Osheius (CEW1) we were able to define a critical period of early development during which worms can learn and memorize short odor inputs. Chemotactic assays performed at the adult stage showed that an early exposure to beta-citronellol or to benzaldehyde, both sensed by the chemosensory neurone AWC, does sensitize worms to these attractants, although sensitizations are restricted to the conditioning concentrations of odorants. As it has been reported for temperature memory, odor memorisation in nematodes is associated with the presence of food. Although starving prevents learning, exogenous serotonine can compensate starvation during the learning phase, and preliminary pharmacological analysis of this experience dependent behaviour identified the octopamine agonist synephrin as an enhancer of olfactive memory. The physiological significance of this behaviour is not known, but one think of fast environmental adaptative processes. It is known that the thermosensory AFD and chemosensory neurones responsible for attraction to volatil attractants, AWA and AWC, cosynapse the same interneurone AIY. Using a candidate gene approach, we found that the two alleles ot-22 and ks-5 of the thermotaxis mutant ttx-3, a LIM homeobox exclusively expressed in AIY (1)), although not affected in their chemotaxis behaviour, unable to perform olfactory learning and memory. Sel-12 mutants (2) , as well as the null mutant for the neuronal calcium sensor NCS-1 (3) both displaying AIY morphological and functional defects, presented olfactory memory impairment. Alltogether, these observations provide new experimental support to the idea of cointegration and memory of thermo and chemosensory inputs in C. elegans (Pierce-Shimomura, IWM 2001), through common involvment of the postsynaptic AIY interneuron. Memory mechanisms at the cellular and molecular levels are not well understood : they can involve the cAMP/CREB pathway, synaptic strength modulations, or establishment of new synapses. Our current view for explaining odorant memory in C. elegans, as it is specific for odorant concentrations, is that it must (at least) rely on odorant specific olfactory receptors expression levels -transcriptional control in the different chemosensory neurones- or/and at the level of efficiency of their individual coupling to the transducing partners. Specific experiments, including microarray approaches, have now to be carried out to verify this hypothesis.