LFRFamides: a novel family of parasitation‐induced ‐RFamide neuropeptides that inhibit the activity of neuroendocrine cells in Lymnaea stagnalis

Abstract

We report the characterization of a cDNA encoding a novel -RFamide neuropeptide precursor that is up-regulated during parasitation in the snail Lymnaea stagnalis. Processing of this precursor yields five structurally related neuropeptides, all but one ending with the C-terminal sequence -LFRFamide, as was confirmed by direct mass spectrometry of brain tissue. The LFRFamide gene is expressed in a small cluster of neurons in each buccal ganglion, three small clusters in each cerebral ganglion, and one cluster in each lateral lobe of the cerebral ganglia. Application of two of the LFRFamide peptides to neuroendocrine cells that control either growth and metabolism or reproduction induced similar hyperpolarizing K + -currents, and inhibited electrical activity. We conclude that up-regulation of inhibitory LFRFamide neuropeptides during parasitation probably reflects an evolutionary adaptation that allows endoparasites to suppress host metabolism and reproduction in order to fully exploit host energy recourses.

Functional characterization of a short neuropeptide F-related receptor in a Lophotrochozoa, the mollusk Crassostrea gigas

“…A perfect match was found for the OYG_10020740 predicted gene, which overlaps with EST CU994925 from nucleotide 156 and was considered to encode the oyster LFRFamide precursor. The deduced precursor protein displays an organization similar to that of the L. stagnalis LFRFamide precursor (Hoek et al, 2005) and consists of 159 amino acids, including a 23 amino acid signal peptide and nine predicted endoproteolytic cleavage sites. Complete processing of the peptide precursor would generate four distinct and likely amidated peptides due to the presence of a C-terminal glycine residue: three LFRFamide hexapeptides (GSLFRFamide, GALFRFamide and SSLFRFamide) and a single FRFamide tridecapeptide (SVDNEKPHTPFRFamide) (Fig.…”

“…In the snail L. stagnalis, an LFRFamide encoding gene was strongly upregulated upon schistosome parasitic infection, a biological event known to disturb host growth, energy metabolism and reproduction (Hoek et al, 1997). Alteration of these functions is thought to result from the inhibitory action of LFRFamide peptides on L. stagnalis caudodorsal and light green cells, two cell clusters that regulate female reproduction, and growth and metabolism, respectively (Hoek et al, 2005). More recently, a new LFRFamide peptide with potent activity on the contraction of the rectum was identified in the cephalopod Sepia officinalis (Zatylny-Gaudin et al, 2010).…”

Avian Schistosomes and Outbreaks of Cercarial Dermatitis

“…As a result, the body size of infected snails may become considerably larger than that of uninfected snails (142, 161). Other neuropeptides (FMRFamide-related peptides) are also upregulated during infection of L. stagnalis by T. szidati, and these peptides, via inhibition of neuroendocrine cells, may be responsible for the suppression of snail metabolism and reproduction (167). All these changes in infected snails may provide energy resources and space that can be exploited by the schistosomes for development (145,161).…”

Identification and characterization of a gonadotropin-inhibitory system in the brains of mammals

“…In summary, RFamide peptides are emerging as important regulators of neuroendocrine function (38,46,47). Our data indicate an important role for the RFRP, GnIH, in regulating the mammalian reproductive axis.…”