cognate receptors

Neuropeptides modulate neural circuits driving adaptive behaviors and key physiological proc-esses such as reproductive behavior, metabolism, feeding, locomotion, and experience-based learning. With over 250 predicted sequences, bioactive peptides are by far the largest and most diverse group of neuromodulatory substances in the C. elegans nervous system (Li and Kim, 2010; Bargmann 2012,). Most of them are thought to function through the activation of G protein-coupled receptors (GPCRs) belonging to the Rhodopsin and Secretin classes. The C. elegans genome encodes at least 120 genes for neuropeptide precursors (FLP, NLP, and INS families), and recent studies have estimated a similar number of about 100 to 150 peptide GPCR genes (Frooninckx et al., 2012; Hobert, 2013). Although peptide signaling has undoubtedly diversified in the nematode lineage, many neuropeptidergic signal-ing systems share homology to vertebrate and protostomian systems (Mirabeau and Joly, 2013). Grow-ing evidence implicates neuropeptides in many, if not all, behaviors in C. elegans. In contrast, only 23 C. elegans peptide GPCRs (isoforms included) have been deorphanized so far (Frooninckx et al., 2012), leaving more than 80 percent of all putative peptide receptors with unknown ligands. Knowledge on functionally active neuropeptide-receptor couples and GPCR affinity is crucial to further expand our understanding of how neuropeptides function and modulate neural circuits. W