Neuropeptide signalling systems in flatworms

Abstract

Two distinct families of neuropeptides are known to endow platyhelminth nervous systems-the FMRFamide-like peptides (FLPs) and the neuropeptide Fs (NPFs). Flatworm FLPs are structurally simple, each 4-6 amino acids in length with a carboxy terminal aromatic-hydrophobic-Arg-Phe-amide motif. Thus far, four distinct flatworm FLPs have been characterized, with only one of these from a parasite. They have a widespread distribution within the central and peripheral nervous system of every flatworm examined, including neurones serving the attachment organs, the somatic musculature and the reproductive system. The only physiological role that has been identified for flatworm FLPs is myoexcitation. Flatworm NPFs are believed to be invertebrate homologues of the vertebrate neuropeptide Y (NPY) family of peptides. Flatworm NPFs are 36-39 amino acids in length and are characterized by a caboxy terminal GRPRFamide signature and conserved tyrosine residues at positions 10 and 17 from the carboxy terminal. Like FLPs, NPF occurs throughout flatworm nervous systems, although less is known about its biological role. While there is some evidence for a myoexcitatory action in cestodes and flukes, more compelling physiological data indicate that flatworm NPF inhibits cAMP levels in a manner that is characteristic of NPY action in vertebrates. The widespread expression of these neuropeptides in flatworm parasites highlights the potential of these signalling systems to yield new targets for novel anthelmintics. Although platyhelminth FLP and NPF receptors await identification, other molecules that play pivotal roles in neuropeptide signalling have been uncovered. These enzymes, involved in the biosynthesis and processing of flatworm neuropeptides, have recently been described and offer other distinct and attractive targets for therapeutic interference.

A review of FMRFamide- and RFamide-like peptides in metazoa

“…The peripheral nervous system is made up of several minor nerve cords, viz, the subepidermal, submuscular, stomatogastric and genital nerve plexi (Gustafsson et al 2002). There have been recent reviews where FLPs in platyhelminths have been discussed, and the reader is referred to them (McVeigh et al 2005a;Mousley et al 2005). Immunoreactivity to antisera raised against vertebrate neuropeptides occurs widely in the platyhelminth nervous system (Halton and Gustafsson 1996).…”

Regenerating the central nervous system: how easy for planarians!

“…Also, immunostaining against gamma-aminobutyric acid (GABA) has been shown in the CNS and the subepidermal plexus of G. tigrina (Eriksson and Panula 1994). Two families of neuropeptides, the FMRFamide-like peptides and the neuropeptide Fs, have been shown to be present in planarians (McVeigh et al 2005). An antiserum against neuropeptide F from Moniezia expansa (Maule et al 1992) labels the CNS and peripheral plexuses (submuscular and pharyngeal) of freshwater (Reuter et al 1995b) and marine (Reuter et al 1995a) planarians.…”

“…Although, at first sight, planarians and their nervous system may appear simple, a closer look reveals greater complexity. This complexity is found at many levels: (1) At the cellular level, we find unipolar, bipolar, and multipolar neurons; (2) at the structural level, different types of vesicles and release sites have been described along with a wide range of neuroactive substances, including serotonin, dopamine, noradrenaline, and several neuropeptides (McVeigh et al 2005;Reuter and Gustafsson 1995;Ribeiro et al 2005); and finally, (3) at the gene level, the first high throughput analyses of the planarian CNS have shown its complexity in the number and degree of conservation of neural specific genes , as well as in the molecular compartmentalization of the planarian CNS (Cebrià et al 2002b;Nakazawa et al 2003;Umesono et al 1999). Despite this weight of accumulated knowledge and the newly available molecular markers, we are still some way from fully understanding how the planarian CNS is regenerated.…”

Neuropeptides regulate swimming depth of Platynereis larvae

“…They are produced from inactive precursor proteins by proteolytic cleavage and further processing (e.g., amidation) (27)(28)(29) and are released into the hemolymph to act as hormones or at synapses to regulate target cells. Neuropeptides have a wide range of functions in the control of neural circuits and physiology, including the modulation of locomotion and rhythmic pattern generators (30)(31)(32)(33), presynaptic facilitation and remodeling of sensory networks (34,35), and the regulation of reproduction (36,37). We have only limited information about the role of neuropeptides in the regulation of ciliary beating (38,39).…”