Discovery and functional characterisation of a luqin-type neuropeptide signalling system in a deuterostome

Luis Alfonso Yañez-Guerra,James H Scrivens,Maurice R Elphick,Susan E Slade,Antón Barreiro-Iglesias,Jérôme Delroisse

doi:10.1038/s41598-018-25606-2

Abstract

Neuropeptides are diverse and evolutionarily ancient regulators of physiological/behavioural processes in animals. Here we have investigated the evolution and comparative physiology of luqin-type neuropeptide signalling, which has been characterised previously in protostomian invertebrates. Phylogenetic analysis indicates that luqin-type receptors and tachykinin-type receptors are paralogous and probably originated in a common ancestor of the Bilateria. In the deuterostomian lineage, luqin-type signalling has been lost in chordates but interestingly it has been retained in ambulacrarians. Therefore, here we characterised luqin-type signalling for the first time in an ambulacrarian – the starfish Asterias rubens (phylum Echinodermata). A luqin-like neuropeptide with a C-terminal RWamide motif (ArLQ; EEKTRFPKFMRW-NH2) was identified as the ligand for two luqin-type receptors in A. rubens, ArLQR1 and ArLQR2. Furthermore, analysis of the expression of the ArLQ precursor using mRNA in situ hybridisation revealed expression in the nervous system, digestive system and locomotory organs (tube feet) and in vitro pharmacology revealed that ArLQ causes dose-dependent relaxation of tube feet. Accordingly, previous studies have revealed that luqin-type signalling regulates feeding and locomotor activity in protostomes. In conclusion, our phylogenetic analysis combined with characterisation of luqin-type signalling in a deuterostome has provided new insights into neuropeptide evolution and function in the animal kingdom.

Highlights

Neuropeptides play a central role in the control of diverse physiological processes and behaviours in animals
Phylogenetic analysis of luqin/RYamide-type precursors revealed that they cluster in three distinct clades: deuterostomian precursors comprising a neuropeptide with a C-terminal RWamide motif, lophotrochozoan precursors comprising one or two neuropeptides with a C-terminal RFamide motif and ecdysozoan precursors comprising two neuropeptides with a C-terminal RYamide motif (Fig. 1C; Supplementary Fig. 1)
To investigate the occurrence of luqin/RYamide-type receptors in A. rubens, we performed a comprehensive analysis of the phylogenetic distribution of luqin/RYamide-type receptors and their relationships with closely related G-protein coupled neuropeptide receptors

Summary

Introduction

Neuropeptides play a central role in the control of diverse physiological processes and behaviours in animals. The mature peptide derived from this precursor was identified biochemically as APSWRPQGRFamide and named luqin (LQ) because it is expressed in the Left Upper Quadrant cells of the abdominal ganglion in A. californica[6] Prior to this a homolog of luqin (SGQWRPQGRFamide) was discovered in the snail Achatina fulica and named Achatina Cardio-Excitatory Peptide (ACEP-1) on account of its effect in potentiating the beat of the heart ventricle in www.nature.com/scientificreports/. The evolutionary origin of luqin/RYamide-type neuropeptide signalling can be traced to common ancestor of protostomes and deuterostomes, but with subsequent loss in the chordate lineage Consistent with this conclusion, precursor proteins comprising candidate ligands for luqin/ RYamide-type receptors have been identified in ambulacrarians but not in chordates[1,22]

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