The Protein Precursors of Peptides That Affect the Mechanics of Connective Tissue and/or Muscle in the Echinoderm Apostichopus japonicus

PMCID: PMC3432112This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

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

Bioactivity and structural properties of chimeric analogs of the starfish SALMFamide neuropeptides S1 and S2

The starfish SALMFamide neuropeptides S1 (GFNSALMFamide) and S2 (SGPYSFNSGLTFamide) are the prototypical members of a family of neuropeptides that act as muscle relaxants in echinoderms. Comparison of the bioactivity of S1 and S2 as muscle relaxants has revealed that S2 is ten times more potent than S1. Here we investigated a structural basis for this difference in potency by comparing the bioactivity and solution conformations (using NMR and CD spectroscopy) of S1 and S2 with three chimeric analogs of these peptides. A peptide comprising S1 with the addition of S2's N-terminal tetrapeptide (Long S1 or LS1; SGPYGFNSALMFamide) was not significantly different to S1 in its bioactivity and did not exhibit concentration-dependent structuring seen with S2. An analog of S1with its penultimate residue substituted from S2 (S1(T); GFNSALTFamide) exhibited S1-like bioactivity and structure. However, an analog of S2 with its penultimate residue substituted from S1 (S2(M); SGPYSFNSGLMFamide) exhibited loss of S2-type bioactivity and structural properties. Collectively, our data indicate that the C-terminal regions of S1 and S2 are the key determinants of their differing bioactivity. However, the N-terminal region of S2 may influence its bioactivity by conferring structural stability in solution. Thus, analysis of chimeric SALMFamides has revealed how neuropeptide bioactivity is determined by a complex interplay of sequence and conformation

The evolution and comparative neurobiology of endocannabinoid signalling

CB(1)- and CB(2)-type cannabinoid receptors mediate effects of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide in mammals. In canonical endocannabinoid-mediated synaptic plasticity, 2-AG is generated postsynaptically by diacylglycerol lipase alpha and acts via presynaptic CB(1)-type cannabinoid receptors to inhibit neurotransmitter release. Electrophysiological studies on lampreys indicate that this retrograde signalling mechanism occurs throughout the vertebrates, whereas system-level studies point to conserved roles for endocannabinoid signalling in neural mechanisms of learning and control of locomotor activity and feeding. CB(1)/CB(2)-type receptors originated in a common ancestor of extant chordates, and in the sea squirt Ciona intestinalis a CB(1)/CB(2)-type receptor is targeted to axons, indicative of an ancient role for cannabinoid receptors as axonal regulators of neuronal signalling. Although CB(1)/CB(2)-type receptors are unique to chordates, enzymes involved in biosynthesis/inactivation of endocannabinoids occur throughout the animal kingdom. Accordingly, non-CB(1)/CB(2)-mediated mechanisms of endocannabinoid signalling have been postulated. For example, there is evidence that 2-AG mediates retrograde signalling at synapses in the nervous system of the leech Hirudo medicinalis by activating presynaptic transient receptor potential vanilloid-type ion channels. Thus, postsynaptic synthesis of 2-AG or anandamide may be a phylogenetically widespread phenomenon, and a variety of proteins may have evolved as presynaptic (or postsynaptic) receptors for endocannabinoids

Structural analysis of the starfish SALMFamide neuropeptides S1 and S2: The N-terminal region of S2 facilitates self-association

The neuropeptides S1 (GFNSALMFamide) and S2 (SGPYSFNSGLTFamide), which share sequence similarity, were discovered in the starfish Asterias rubens and are prototypical members of the SALMFamide family of neuropeptides in echinoderms. SALMFamide neuropeptides act as muscle relaxants and both S1 and S2 cause relaxation of cardiac stomach and tube foot preparations in vitro but S2 is an order of magnitude more potent than S1. Here we investigated a structural basis for this difference in potency using spectroscopic techniques. Circular dichroism spectroscopy showed that S1 does not have a defined structure in aqueous solution and this was supported by 2D nuclear magnetic resonance experiments. In contrast, we found that S2 has a well-defined conformation in aqueous solution. However, the conformation of S2 was concentration dependent, with increasing concentration inducing a transition from an unstructured to a structured conformation. Interestingly, this property of S2 was not observed in an N-terminally truncated analogue of S2 (short S2 or SS2; SFNSGLTFamide). Collectively, the data obtained indicate that the N-terminal region of S2 facilitates peptide self-association at high concentrations, which may have relevance to the biosynthesis and/or bioactivity of S2 in vivo

NG peptides: A novel family of neurophysin-associated neuropeptides

NOTICE: this is the author’s version of a work that was accepted for publication in GENE. 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 GENE, [VOL 458, ISSUE 1-2, (2010)] DOI: 10.1016/j.gene.2010.03.00

Identification of novel SALMFamide neuropeptides in the starfish Marthasterias glacialis

Abstract The SALMFamides are a family of neuropeptides found in species belonging to the phylum Echinodermata and which act as muscle relaxants. The first two members of this family to be identified were both isolated from the starfishes Asterias rubens and Asterias forbesi and are known as S1 (GFNSALMFamide) and S2 (SGPYSFNSGLTFamide). However, little is known about the occurrence and characteristics of SALMFamide neuropeptides in other starfish species. Here we report the identification of four SALMFamide neuropeptides in the starfish Marthasterias glacialis: GFNSALMFamide (S1), SGPYSMTSGLTFamide (MagS2), AYHSALPFamide (MagS3), and AYQTGLPFamide (MagS4). Analysis of the effects of MagS2 and MagS3 on cardiac stomach preparations from Asterias rubens revealed that both peptides cause dose-dependent relaxation, consistent with previous studies using S1 and S2. The identification of four SALMFamide neuropeptides in Marthasterias glacialis provides new insights into the diversity and phylogenetic distribution of SALMFamide neuropeptides in the class Asteroidea of the phylum Echinodermata. In particular, the identification of MagS3 and MagS4, in addition to S1 and the S2-like peptide MagS2, has revealed a greater diversity of SALMFamide neuropeptides occurring in a starfish species than any previous studies

The neuropeptidome of the Crown-of-Thorns Starfish, Acanthaster planci

This study was supported by funds from the Australian federal government Department of the Environment Reef Rescue ‘Caring for Country’ program for funding the ‘The Crown-of-Thorns secretome: Towards a control technology’ project (M. R. H., S. C.). M.R.E. was supported by grants from the BBSRC (BB/M001644/1) and Leverhulme Trust (RPG-2013-351)