From gonadotropin-inhibitory hormone to SIFamides: Are echinoderm SALMFamides the “missing link” in a bilaterian family of neuropeptides that regulate reproductive processes?

• Echinoderm SALMFamides are structurally similar to GnIH/SIFamide-type neuropeptides.
• GnIH/SALMFamide/SIFamide-type neuropeptides inhibit reproductive processes.
• GnIH, SALMFamides and SIFamides are members of a bilaterian neuropeptide family.

Gonadotropin-inhibitory hormone (GnIH) belongs to a family of vertebrate neuropeptides with a C-terminal PxRFamide motif, which exert effects by activating the G-protein coupled receptors NPFF1 and/or NPFF2. Comparative analysis of genome sequence data has revealed that orthologs of NPFF1/NPFF2-type receptors occur throughout the Bilateria and the neuropeptide ligand that activates the Drosophila NPFF1/NPFF2-type receptor has been identified as AYRKPPFNGSIFamide (“SIFamide”). Therefore, SIFamide-type neuropeptides, which occur throughout protostomian invertebrates, probably share a common evolutionary origin with vertebrate PxRFamide-type neuropeptides. Based on structural similarities, here SALMFamide neuropeptides are identified as candidate ligand components of this ancient bilaterian peptide-receptor signaling system in a deuterostomian invertebrate phylum, the echinoderms (e.g., starfish, sea urchins). Furthermore, functional studies provide evidence that PxRFamide/SALMFamide/SIFamide-type neuropeptides have evolutionarily conserved roles in regulation (typically inhibitory) of reproductive processes.