In our new preprint we characterise neuropeptide signalling in the cnidarian .
biorxiv.org/content/10.1101/20
Daniel Thiel and Luis Yanez-Guerra screened 64 neuropeptides against 161 G-protein coupled receptors () and found activating peptide ligands for 31 receptors.

Large-scale deorphanization of Nematostella vectensis neuropeptide GPCRs supports the independent expansion of bilaterian and cnidarian peptidergic systems

Neuropeptides are ancient signaling molecules in animals but only few peptide receptors are known outside bilaterians. Cnidarians possess a large number of G protein-coupled receptors (GPCRs), the most common receptors of bilaterian neuropeptides, but most of these remain orphan with no known ligands. We searched for neuropeptides in the sea anemone Nematostella vectensis and created a library of 64 peptides derived from 33 precursors. In a large-scale pharmacological screen with these peptides and 161 N. vectensis GPCRs, we identified 31 receptors specifically activated by one of 14 peptides. Mapping GPCR and neuropeptide expression to single-cell sequencing data revealed how cnidarian tissues are extensively wired by multilayer peptidergic networks. Phylogenetic analysis identified no direct orthology to bilaterian peptidergic systems and supports the independent expansion of neuropeptide signaling in cnidarians from a few ancestral peptide-receptor pairs. ### Competing Interest Statement The authors have declared no competing interest.

www.biorxiv.org

To get a comprehensive list of , we combined screening and mass spectrometry in collaboration with Amanda Kieswetter and Liesbet Temmerman at KU Leuven. We found 15 new proneuropeptides and confirmed the endogenous processing (cleavage, amidation etc) of many of them. has at least 33 neuropeptide precursors.

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