System-wide mapping of peptide-GPCR interactions in C. elegans.

Neuropeptides and peptide hormones are ancient, widespread signaling molecules that underpin almost all brain functions. They constitute a broad ligand-receptor network, mainly by binding to G protein-coupled receptors (GPCRs). However, the organization of the peptidergic network and roles of many peptides remain elusive, as our insight into peptide-receptor interactions is limited and many peptide GPCRs are still orphan receptors. Here we report a genome-wide peptide-GPCR interaction map in Caenorhabditis elegans. By reverse pharmacology screening of over 55,384 possible interactions, we identify 461 cognate peptide-GPCR couples that uncover a broad signaling network with specific and complex combinatorial interactions encoded across and within single peptidergic genes. These interactions provide insights into peptide functions and evolution. Combining our dataset with phylogenetic analysis supports peptide-receptor co-evolution and conservation of at least 14 bilaterian peptidergic systems in C. elegans. This resource lays a foundation for system-wide analysis of the peptidergic network.

Regulation of Feeding and Metabolism by Neuropeptide F and Short Neuropeptide F in Invertebrates.

Numerous neuropeptide systems have been implicated to coordinately control energy homeostasis, both centrally and peripherally. However, the vertebrate neuropeptide Y (NPY) system has emerged as the best described one regarding this biological process. The protostomian ortholog of NPY is neuropeptide F, characterized by an RXRF(Y)amide carboxyterminal motif. A second neuropeptide system is short NPF, characterized by an M/T/L/FRF(W)amide carboxyterminal motif. Although both short and long NPF neuropeptide systems display carboxyterminal sequence similarities, they are evolutionary distant and likely already arose as separate signaling systems in the common ancestor of deuterostomes and protostomes, indicating the functional importance of both. Both NPF and short-NPF systems seem to have roles in the coordination of feeding across bilaterian species, but during chordate evolution, the short NPF system appears to have been lost or evolved into the prolactin releasing peptide signaling system, which regulates feeding and has been suggested to be orthologous to sNPF. Here we review the roles of both NPF and sNPF systems in the regulation of feeding and metabolism in invertebrates.