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Front Neurosci
2020 Feb 18;14:130. doi: 10.3389/fnins.2020.00130.
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Evolution and Comparative Physiology of Luqin-Type Neuropeptide Signaling.
Yañez-Guerra LA
,
Elphick MR
.
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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.
FIGURE 1. Alignment of the N-terminal neuropeptide-containing and C-terminal regions of luqin-type precursor proteins in bilaterians. Conserved residues are highlighted in black or gray. The C-terminal residues of the luqin-type neuropeptides and species names are highlighted in phylum-specific colors: red (Mollusca), pink (Annelida), orange (Platyhelminthes, Brachiopods, and Nemerteans), green (Arthropoda), purple (Nematoda), yellow (Priapulida and Tardigrada), light blue (Echinodermata), and dark blue (Hemichordata). Species names are as follows: Acal (Aplysia californica), Aful (Achatina fulica), Cgig (Crassostrea gigas), Iobs (Ilyanasa obsoleta), Bgla (Biomphalaria glabrata), Ctel (Capitella teleta), Smed (Schmidtea mediterranea), Lana (Lingula anatina), Llon (Lineus longissimus), Dmel (Drosophila melanogaster), Aaeg (Aedes aegypti), Tcas (Tribolium castaneum), Cqua (Cherax quadricarinatus) Tsui (Trichuris suis), Cele (Caenorhabditis elegans), Pcau (Priapulus caudatus), Hduj (Hypsibius dujardini), Rvar (Ramazzottius varieornatus), Arub (Asterias rubens), Ovic (Ophionotus victoriae), Ajap (Apostichopus japonicus), Spur (Strongylocentrotus purpuratus), Skow (Saccoglossus kowalevskii). The sequences used for this alignment were reported in Koziol et al. (2016); Koziol (2018), Yañez-Guerra et al. (2018), and De Oliveira et al. (2019).
FIGURE 2. Phylogenetic tree showing the occurrence and relationships of luqin/RYamide-type receptors and tachykinin-type receptors in bilaterians. The tree comprises two distinct receptor clades—luqin/RYamide-type receptors and the paralogous tachykinin-type receptors, with thyrotropin-releasing hormone (TRH)-type receptors included as an outgroup. Taxa are color-coded and SH-aLRT support (Guindon et al., 2010) [1000 replicates] for clades is represented with colored stars, as explained in the key. Species in which the peptide ligands that activate luqin/RYamide-type receptors or tachykinin-type receptors have been identified experimentally are shown with blue lettering. Species names are as follows: Aaeg (Aedes aegypti), Acal (Aplysia californica), Apis (Acyrthosiphon pisum), Arub (Asterias rubens), Cele (Caenorhabditis elegans), Cint (Ciona intestinalis), Ctel (Capitella teleta), Dmel (Drosophila melanogaster), Hduj (Hypsibius dujardini), Hsap (Homo sapiens), Lana (Lingula anatina), Lsta (Lymnaea stagnalis), Obim (Octopus bimaculoides), Ovul (Octopus vulgaris), Pcau (Priapulus caudatus), Pdum (Platynereis dumerilii), Rvar (Ramazzottius varieornatus), Skow (Saccoglossus kowalevskii), Spur (Strongylocentrotus purpuratus), Tcas (Tribolium castaneum), Tsui (Trichuris suis), Tpse (Trichinella pseudospiralis), Uuni (Urechis unicinctus). This figure is a modified version of a tree reported previously in Yañez-Guerra et al. (2018), with the addition of published luqin-type receptor sequences from the tardigrades H. dujardini and R. varieornatus (Koziol, 2018) and the brachiopod L. anatina (XP_013402794.1, XP_013402807.1) and tachykinin-type receptor sequences from the nematodes C. elegans (tk-1; C38C10.1) (Mirabeau and Joly, 2013) and T. spiralis (KRY8989.1). The alignment was performed using MUSCLE (Edgar, 2004) [16 iterations] and the trimming was made using BMGE (Criscuolo and Gribaldo, 2010) [standard automatic trimming]. The tree was generated in W-IQ-tree (Trifinopoulos et al., 2016) using the maximum likelihood method with automatic selection of the substitution model. The branch support analysis used was SH-aLRT (Guindon et al., 2010) with 1000 iterations.
FIGURE 3. Phylogenetic diagram showing the occurrence of luqin-type neuropeptide signaling in the Bilateria. The phylogenetic tree shows relationships of selected bilaterian phyla. The phyla in which luqin-type precursors and luqin-type receptors have been identified are labeled with purple-filled boxes. The number in the precursor box indicates how many luqin-type neuropeptides are known or predicted to be derived from the precursor protein. The inclusion of a plus symbol in the receptor boxes indicates that the peptide ligand(s) that activates the receptor has been determined experimentally. Note the loss of the luqin-type signaling system in the chordate lineage, which is signified by the red cross and the white-filled boxes. Note that Xenacoelomorpha are not included in this diagram because of the controversy regarding the phylogenetic position of this phylum. However, as discussed in this review, luqin-type receptors have been identified in xenacoelomorphs but the precursors of peptides that act as ligands for these receptors have yet to be identified. The cladogram depicting bilaterian relationships is based on a recent phylogenetic study reported by Laumer et al. (2019).
FIGURE 4. Summary of the properties and functions of luqin-type neuropeptide signaling in species belonging to four phyla. (A) Mollusca (Lymnaea stagnalis), (B) Arthropoda (Drosophila melanogaster), (C) Nematoda (Caenorhabditis elegans), and (D) Echinodermata (Asterias rubens). The photographs of the animals shown in A–D were taken by Michael Crossley (University of Sussex, United Kingdom), Marycruz Flores-Flores (Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico), Marina Ezcurra (University of Kent, United Kingdom), and Ray Crundwell (Queen Mary University of London, United Kingdom).
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