Dual signaling of Wamide myoinhibitory peptides through a peptide‐gated channel and a GPCR in Platynereis

What is it about?

Neuropeptides represent the largest group of signaling molecules produced by neurons in the nervous system. These short peptides signal to target cells that express specific receptors. These receptors most commonly belong to the family of G-protein coupled receptors (GPCRs). Once a neuropeptide binds to and activates a GPCR, this leads to the alteration of the target cell's activity through a biochemical cascade. This type of signaling is called metabotropic signaling. In some mollusks and cnidarians, some neuropeptides signal through a different class of receptors called peptide-gated ion channels. These channels mediate fast ionotropic signals when their neuropeptide ligand is bound to them. All peptide gated ion channels described so far had neuropeptide ligands distinguished by an RFamide motif. Here we identified and characterized a peptide-gated channel in the marine annelid Platynereis dumerilii that is specifically activated by a different class of peptides called myoinhibitory peptides characterized by a Wamide motif. The identification of a Wamide-gated channel suggests that peptide-gated channels are more diverse and widespread in animals than previously appreciated. We have also shown previously that Platynereis myoinhibitory peptides also activate a GPCR. The myoinhibitory peptide signaling system in Platynereis represents the first example where the same neuropeptides can signal both through an ionotropic and a metabotropic receptor. We also show that the two types of receptors are expressed in different populations of target cells. These findings highlight an additional level of complexity in peptidergic signaling.

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