Review
SALMFamide salmagundi: The biology of a neuropeptide family in echinoderms

https://doi.org/10.1016/j.ygcen.2014.02.012Get rights and content

Highlights

  • First review on SALMFamide neuropeptides, covering 25 years of research.

  • Presents data from all five extant echinoderm classes.

  • Highlights the diversity of SALMFamides that are derived from precursor proteins.

  • Discusses objectives for research on SALMFamides in the future.

Abstract

The SALMFamides are a family of neuropeptides that occur in species belonging to the phylum Echinodermata. The prototypes for this neuropeptide family (S1 and S2) were discovered in starfish but subsequently SALMFamides were identified in other echinoderms. There are two types of SALMFamides: L-type, which have the C-terminal motif SxLxFamide, and F-type, which have the C-terminal motif SxFxFamide. They are derived from two types of precursor proteins: an L-type SALMFamide precursor, which comprises only L-type or L-type-like SALMFamides and an F-type SALMFamide precursor, which contains several F-type or F-type-like SALMFamides and, typically, one or more L-type SALMFamides. Thus, SALMFamides occur as heterogeneous mixtures of neuropeptides – a SALMFamide salmagundi. SALMFamides are produced by distinct populations of neurons in echinoderm larval and adult nervous systems and are present in the innervation of neuromuscular organs. Both L-type and F-type SALMFamides cause muscle relaxation in echinoderms and, for example, in starfish this effect of SALMFamides may mediate neural control of cardiac stomach eversion in species that feed extra-orally (e.g., Asterias rubens). The SALMFamide S1 also causes inhibition of neural release of a relaxin-like gonadotropin in the starfish Asterina pectinifera. An important issue that remains to be resolved are the relationships of SALMFamides with neuropeptides that have been identified in other phyla. However, it has been noted that the C-terminal SxLxFamide motif of L-type SALMFamides is a feature of some members of a bilaterian neuropeptide family that includes gonadotropin-inhibitory hormone (GnIH) in vertebrates and SIFamide-type neuropeptides in protostomes. Similarly, the C-terminal FxFamide motif of F-type SALMFamides is a feature of vertebrate QRFP (26RFa)-type neuropeptides. These sequence similarities may provide a basis for molecular identification of receptors that mediate effects of SALMFamides. Furthermore, analysis of the actions of the heterogeneous mixtures of SALMFamides that occur in echinoderms may provide new insights into the physiological significance of the general phenomenon of precursor proteins that give rise to neuropeptide “cocktails”.

Introduction

Twenty-five years ago a paper reporting “FMRFamide-like immunoreactivity in the nervous system of the starfish Asterias rubens” was published in Biological Bulletin (Elphick et al., 1989). When the paper was submitted for peer review, the feedback from reviewers was supportive but the tone leaned towards “yet another paper reporting FMRFamide-like immunoreactivity in an invertebrate!” This was not unreasonable because by 1989, twelve years after FMRFamide was identified as a cardioexcitatory neuropeptide in molluscs (Price and Greenberg, 1977), there was already a long list of species and phyla in which the presence of FMRFamide-like immunoreactivity had been reported (Price and Greenberg, 1989). In fact, a paper reporting the absence of FMRFamide-like immunoreactivity in starfish would have been more surprising! What made the paper of interest was that it was the first to reveal the anatomical distribution of any neuropeptide(s) in the nervous system of an echinoderm. Furthermore, it laid the foundations for discovery of the first neuropeptides to be identified in echinoderms, SALMFamide neuropeptides, which are the focus of this review article.

The review is divided into five main sections corresponding to the five classes of extant echinoderms. The Asteroidea (starfish) lead the review because it was in species belonging to this class (A. rubens and Asterias forbesi) that SALMFamide neuropeptides (S1 and S2) were first identified (Elphick et al., 1991a). The Holothuroidea follow because soon after the discovery of S1 and S2, two SALMFamide neuropeptides were identified in the sea cucumber Holothuria glaberrima (Díaz-Miranda et al., 1992), providing the first evidence that SALMFamides may occur throughout the phylum Echinodermata. Then come the Echinoidea, which through analysis of genome/transcriptome data from the sea urchin Strongylocentrotus purpuratus provided the first insights into the diversity of SALMFamides that occur in an echinoderm species (Elphick and Thorndyke, 2005, Rowe and Elphick, 2010). Lastly the Ophiuroidea and Crinoidea, the two echinoderm classes for which least is currently known but which have the potential to provide fascinating insights into the evolution and physiological roles of SALMFamide neuropeptides.

Before proceeding, perhaps an explanation for the title of this review is necessary. The word salmagundi is thought to originate from the French word salmigondis, which translates as “an assortment” or “a collection containing a variety of things”. In English the word salmagundi has become associated with a 17th century salad dish comprising a rich variety of ingredients including meats, seafood, nuts, fruit, vegetables etc. However, like its French counterpart, salmagundi also has the more general meaning of a “heterogeneous mixture”. As described in more detail below, genome sequence data and/or transcriptome sequence data have revealed that there are indeed heterogeneous mixtures of SALMFamide neuropeptides in echinoderms. Thus, there are both L-type SALMFamides and F-type SALMFamides; L-type SALMFamides are derived from L-type SALMFamide precursors and F-type SALMFamides are derived from F-type SALMFamide precursors but in some cases F-type SALMFamide precursors also give rise to L-type SALMFamides. Furthermore, there are SALMFamides that are not strictly L-type but are L-type-like and there are SALMFamides that are not strictly F-type but are F-type-like (Elphick et al., 2013). This is the SALMFamide salmagundi; a lexiconic marriage just waiting to happen!

Section snippets

FMRFamide-like immunoreactivity in the nervous system of the starfish A. rubens

In order that patterns of neuropeptide expression in starfish and other echinoderms can be described, it is necessary to first briefly outline the architecture of the nervous systems in these animals. The organisation of the nervous system in adult starfish reflects its pentaradial body plan; there are five radial nerve cords that extend along the midline of each arm linked by a circumoral nerve ring in the central disk. The radial nerve cords control the activity of rows of tube feet that

FMRFamide-like immunoreactivity in sea cucumbers

The presence of FMRFamide-like ir in sea cucumbers was first reported in an immunocytochemical study of H. glaberrima (García-Arrarás et al., 1991). Immunostained neuronal somata and fibres were observed in the radial nerve cords, oesophagus and both the large and small intestine. Interestingly, many of the FMRFamide-like immunoreactive fibres in the digestive tract were also immunoreactive with antibodies to cholecystokinin (CCK), which shares C-terminal sequence similarity (MDFamide) with FMR

SALMFamide-like immunoreactive peptides in the sea urchin Echinus esculentus

The development of radioimmunoassays for the starfish SALMFamides S1 and S2, as described above in Section 2.2 above, facilitated investigation of the occurrence of structurally related SALMFamides in other echinoderms. With SALMFamides having already been identified in a holothurian species (see Section 3.2 above), effort was focused on a species belonging to the class Echinoidea, the sea urchin E. esculentus (Elphick and Thorndyke, 2005). Because it is difficult to dissect nerves from sea

Detection of SALMFamide-like immunoreactive peptides in ophiuroids

In parallel with studies using antibodies to S1 and/or S2 to assay for SALMFamide-type neuropeptides in the sea urchin E. esculentus (see Section 4.1 above), extracts of the brittle star Ophiura ophiura were analysed using the same methodology. S1-like-ir was detected in a range of HPLC-separated fractions but the levels of immunoreactivity were not sufficient to enable purification and sequencing of the immunoreactive peptides (Elphick, 1991). S1-like-ir and S2-like-ir have also been detected

Crinoidea

Currently, very little is known about SALMFamides in crinoids. An immunocytochemical study of pinnules from the crinoid Antedon bifida using antibodies to the starfish SALMFamide neuropeptide S2 revealed groups of S2-like immunoreactive bipolar and roundish neuronal somata (∼6 μm diameter) located at the periphery of pinnular sections of the brachial nerve just before the nerve enters the ossicles (Heinzeller and Welsch, 1994). These cells have processes that project along the boundary between

Conclusions and directions for future research

Looking back over a research programme that was initiated twenty-five years ago, it is timely to assess the broader impact of the discovery of SALMFamide neuropeptides. Perhaps the greatest impact has been providing new tools (in the form of antibodies) for visualisation of echinoderm nervous systems. In particular, antibodies to the starfish SALMFamide neuropeptide S1 have been widely used to reveal for the first time the architecture of neuropeptidergic systems in a variety of echinoderms,

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