Evolution and Comparative Physiology of Luqin-Type Neuropeptide Signaling

Abstract

Luqin is a neuropeptide that was discovered and named on account of its expression in left upper quadrant cells of the abdominal ganglion in the mollusc Aplysia californica. Subsequently, luqin-type peptides were identified as cardio-excitatory neuropeptides in other molluscs and a cognate receptor was discovered in the pond snail Lymnaea stagnalis. Phylogenetic analyses have revealed that orthologs of molluscan luqin-type neuropeptides occur in other phyla; these include neuropeptides in ecdysozoans (arthropods, nematodes) that have a C-terminal RYamide motif (RYamides) and neuropeptides in ambulacrarians (echinoderms, hemichordates) that have a C-terminal RWamide motif (RWamides). Furthermore, precursors of luqin-type neuropeptides typically have a conserved C-terminal motif containing two cysteine residues, although the functional significance of this is unknown. Consistent with the orthology of the neuropeptides and their precursors, phylogenetic and pharmacological studies have revealed that orthologous G-protein coupled receptors (GPCRs) mediate effects of luqin-type neuropeptides in spiralians, ecdysozoans, and ambulacrarians. Luqin-type signaling originated in a common ancestor of the Bilateria as a paralog of tachykinin-type signaling but, unlike tachykinin-type signaling, luqin-type signaling was lost in chordates. This may largely explain why luqin-type signaling has received less attention than many other neuropeptide signaling systems. However, insights into the physiological actions of luqin-type neuropeptides (RYamides) in ecdysozoans have been reported recently, with roles in regulation of feeding and diuresis revealed in insects and roles in regulation of feeding, egg laying, locomotion, and lifespan revealed in the nematode Caenorhabditis elegans. Furthermore, characterization of a luqin-type neuropeptide in the starfish Asterias rubens (phylum Echinodermata) has provided the first insights into the physiological roles of luqin-type signaling in a deuterostome. In conclusion, although luqin was discovered in Aplysia over 30 years ago, there is still much to be learnt about luqin-type neuropeptide signaling. This will be facilitated in the post-genomic era by the emerging opportunities for experimental studies on a variety of invertebrate taxa.

Activation of Bombyx mori neuropeptide G protein–coupled receptor A19 by neuropeptide RYamides couples to Gq protein‐dependent signaling pathways

“…RYamides represent a distinct group of luqin/RYamide‐type neuropeptides identified in insects, and this luqin/RYamide signaling system widely occurs in other invertebrates including crustaceans, mollusks, nematodes, and echinoderms but have been lost in vertebrates 4,8,16,34–36 . However, our understanding of their signaling and physiological role is still very limited.…”

Nemertean, brachiopod and phoronid neuropeptidomics reveals ancestral spiralian signalling systems

“…2) and manual curation (see Supplementary Material 1). To assess potential homologies between certain pNPs, we carried out gene structure analyses, which proved to be a powerful tool in homology assessments for neuropeptide precursors (Mair et al, 2000;Yañez-Guerra et al, 2020;Zhang et al, 2020). With this comprehensive strategy, we identified a total of approximately 1,300 potential neuropeptide precursor candidates including different paralogs and isoforms (Supplementary Material 1, 2).…”

“…The longer (several hundred amino acids) and more conserved sequence of GPCRs make phylogenetic analyses feasible when reconstructing the evolution of peptidergic systems (Jekely, 2013;Mirabeau and Joly, 2013). Another useful approach is to compare the exon-intron structure of pNPs (Mair et al, 2000;Yañez-Guerra et al, 2020;Zhang et al, 2020). In several cases, the overall organisation of orthologous pNP genes can be conserved (e.g.…”

“…a region coding for the signal peptide followed by a single peptide and a C-terminal Cys-containing domain) (Semmens et al, 2015;Liutkeviciute et al, 2016). Furthermore, an increased sampling across taxa has often helped to clarify relationships, revealing hidden orthologs or lineage specific losses, gains and divergences (Jekely, 2013;Mirabeau and Joly, 2013;Semmens et al, 2016;Martín-Durán et al, 2017;Thiel et al, 2018;Yañez-Guerra et al, 2020). Some lineages can retain signalling systems that had been lost in related species.…”

“…For example, corazonin, luqin and short neuropeptide F are widespread neuropeptides in protostomes but not detectable in vertebrates. These pNPs and their receptors are, however, present in ambulacrarians like the hemichordate Saccoglossus kovalevski or the starfish Asterias rubens, indicating that they represent ancestral bilaterian signaling systems (Tian et al, 2016;Yañez-Guerra et al, 2018Yañez-Guerra and Elphick, 2020). Among the lophotrochozoans, a major and diverse clade of bilaterians, the study of neuropeptides has mostly been limited to molluscs (Veenstra, 2010;Stewart et al, 2014;Adamson et al, 2015;Bose et al, 2017;Oliveira et al, 2019) and annelids (Veenstra, 2011;Conzelmann, Williams, Krug, et al, 2013;Kerbl et al, 2017).…”