The evolution and variety of RFamide-type neuropeptides: insights from deuterostomian invertebrates

Five families of neuropeptides that have a C-terminal RFamide motif have been identified in vertebrates: (1) gonadotropin-inhibitory hormone (GnIH), (2) neuropeptide FF (NPFF), (3) pyroglutamylated RFamide peptide (QRFP), (4) prolactin-releasing peptide (PrRP), and (5) Kisspeptin. Experimental demonstration of neuropeptide–receptor pairings combined with comprehensive analysis of genomic and/or transcriptomic sequence data indicate that, with the exception of the deuterostomian PrRP system, the evolutionary origins of these neuropeptides can be traced back to the common ancestor of bilaterians. Here, we review the occurrence of homologs of vertebrate RFamide-type neuropeptides and their receptors in deuterostomian invertebrates – urochordates, cephalochordates, hemichordates, and echinoderms. Extending analysis of the occurrence of the RFamide motif in other bilaterian neuropeptide families reveals RFamide-type peptides that have acquired modified C-terminal characteristics in the vertebrate lineage (e.g., NPY/NPF), neuropeptide families where the RFamide motif is unique to protostomian members (e.g., CCK/sulfakinins), and RFamide-type peptides that have been lost in the vertebrate lineage (e.g., luqins). Furthermore, the RFamide motif is also a feature of neuropeptide families with a more restricted phylogenetic distribution (e.g., the prototypical FMRFamide-related neuropeptides in protostomes). Thus, the RFamide motif is both an ancient and a convergent feature of neuropeptides, with conservation, acquisition, or loss of this motif occurring in different branches of the animal kingdom

DINeR: Database for Insect Neuropeptide Research

Neuropeptides are responsible for regulating a variety of functions, including development, metabolism, water and ion homeostasis, and as neuromodulators in circuits of the central nervous system. Numerous neuropeptides have been identified and characterized. However, both discovery and functional characterization of neuropeptides across the massive Class Insecta has been sporadic. To leverage advances in post-genomic technologies for this rapidly growing field, insect neuroendocrinology requires a consolidated, comprehensive and standardised resource for managing neuropeptide information. The Database for Insect Neuropeptide Research (DINeR) is a web-based database-application used for search and retrieval of neuropeptide information of various insect species detailing their isoform sequences, physiological functionality and images of their receptor-binding sites, in an intuitive, accessible and user-friendly format. The curated data includes representatives of 50 well described neuropeptide families from over 400 different insect species. Approximately 4700 FASTA formatted, neuropeptide isoform amino acid sequences and over 200 records of physiological functionality have been recorded based on published literature. Also available are images of neuropeptide receptor locations. In addition, the data include comprehensive summaries for each neuropeptide family, including their function, location, known functionality, as well as cladograms, sequence alignments and logos covering most insect orders. Moreover, we have adopted a standardized nomenclature to address inconsistent classification of neuropeptides

An opioid-like system regulating feeding behavior in C. elegans

Neuropeptides are essential for the regulation of appetite. Here we show that neuropeptides could regulate feeding in mutants that lack neurotransmission from the motor neurons that stimulate feeding muscles. We identified nlp-24 by an RNAi screen of 115 neuropeptide genes, testing whether they affected growth. NLP-24 peptides have a conserved YGGXX sequence, similar to mammalian opioid neuropeptides. In addition, morphine and naloxone respectively stimulated and inhibited feeding in starved worms, but not in worms lacking NPR-17, which encodes a protein with sequence similarity to opioid receptors. Opioid agonists activated heterologously expressed NPR-17, as did at least one NLP-24 peptide. Worms lacking the ASI neurons, which express npr-17, did not response to naloxone. Thus, we suggest that Caenorhabditis elegans has an endogenous opioid system that acts through NPR-17, and that opioids regulate feeding via ASI neurons. Together, these results suggestC. elegans may be the first genetically tractable invertebrate opioid model

Molecular Aspect of Annelid Neuroendocrine system

Hormonal processes along with enzymatic processing similar to that found in vertebrates occur in annelids. Amino acid sequence determination of annelids precursor gene products reveals the presence of the respective peptides that exhibit high sequence identity to their mammalian counterparts. Furthermore, these neuropeptides exert similar physiological function in annelids than the ones found in vertebrates. In this respect, the high conservation in course of evolution of these molecules families reflects their importance. Nevertheless, some specific neuropeptides to annelids or invertebrates have also been in these animals

The Evolution and Diversity of SALMFamide Neuropeptides

The SALMFamides are a family of neuropeptides that act as muscle relaxants in echinoderms. Two types of SALMFamides have been identified: L-type (e.g. the starfish neuropeptides S1 and S2) with the C-terminal motif LxFamide (x is variable) and F-type with the C-terminal motif FxFamide. In the sea urchin Strongylocentrotus purpuratus (class Echinoidea) there are two SALMFamide genes, one encoding L-type SALMFamides and a second encoding F-type SALMFamides, but hitherto it was not known if this applies to other echinoderms. Here we report the identification of SALMFamide genes in the sea cucumber Apostichopus japonicus (class Holothuroidea) and the starfish Patiria miniata (class Asteroidea). In both species there are two SALMFamide genes: one gene encoding L-type SALMFamides (e.g. S1 in P. miniata) and a second gene encoding F-type SALMFamides plus one or more L-type SALMFamides (e.g. S2-like peptide in P. miniata). Thus, the ancestry of the two SALMFamide gene types traces back to the common ancestor of echinoids, holothurians and asteroids, although it is not clear if the occurrence of L-type peptides in F-type SALMFamide precursors is an ancestral or derived character. The gene sequences also reveal a remarkable diversity of SALMFamide neuropeptides. Originally just two peptides (S1 and S2) were isolated from starfish but now we find that in P. miniata, for example, there are sixteen putative SALMFamide neuropeptides. Thus, the SALMFamides would be a good model system for experimental analysis of the physiological significance of neuropeptide "cocktails" derived from the same precursor protein

Discovery of a second SALMFamide gene in the sea urchin Strongylocentrotus purpuratus reveals that L-type and F-type SALMFamide neuropeptides coexist in an echinoderm species

NOTICE: this is the author’s version of a work that was accepted for publication in MARINE GENOMICS. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in MARINE GENOMICS, [VOL 3, ISSUE 2, (2010)] DOI: 10.1016/j.margen.2010.08.00

The neuropeptide transcriptome of a model echinoderm, the sea urchin Strongylocentrotus purpuratus

The work reported here was supported by a grant from the University of London Central Research Fun

Capillary HPLC Separation of Selected Neuropeptides

Neuropeptides play a pivotal role in brain and peripheral nervous system function. As high performance liquid chromatography (HPLC) becomes the central tool in the separation and characterization of peptide and protein samples, its selectivity optimization has attracted increasing attention. This research program aims to develop useful, quantitative analysis methods for neuropeptides and their hydrolysis fragments by capillary HPLC. Related peptide pairs are successfully separated, such as leu-enkephalin and [Des-Tyr1] leu-enkephalin, dynorphin A and dynorphin B, galanin and its fragment Gal1-16. The hydrolysis of leu-enkephalin to [Des-Tyr1] leu-enkephalin by organotypic hippocampal slice cultures (OHSCs) can be monitored by the same HPLC system. The separation of seven hippocampal neuropeptides with similar hydrophobicity, Bj-PRO-5a, [Des-Tyr1] leu-enkephalin, leu-enkephalin, pentagastrin, Antho-RW-amide I, dynorphin A 1-6 and angiotensin II, is accomplished by thermally tuned tandem capillary columns (T3C). The chromatographic selectivity is continuously, systematically and significantly optimized by individual adjustment of each column’s temperature. The T3C concept is applied for the first time with capillary columns, which is an important step towards optimization of selectivity for separations of small samples by liquid chromatography

From obesity resistance to obesity prediction and prevention?

Comment on: Regulation of hypothalamic neuropeptides gene expression in diet induced obesity resistant rats: possible targets for obesity prediction? [Front Neurosci. 2015