Abstract
FMRFamide-like peptide (FLP) signalling systems are core to nematode neuromuscular function. Novel drug discovery efforts associated with nematode FLP/FLP receptor biology are advanced through the accumulation of basic biological data that can reveal subtle complexities within the neuropeptidergic system. This study reports the characterisation of FMRFamide-like peptide encoding gene-11 (flp-11) and FMRFamide-like peptide encoding gene-32 (flp-32), two distinct flp genes which encode the analogous peptide, AMRN(A/S)LVRFamide, in multiple nematode species – the only known example of this phenomenon within the FLPergic system of nematodes. Using bioinformatics, in situ hybridisation, immunocytochemistry and behavioural assays we show that: (i) flp-11 and -32 are distinct flp genes expressed individually or in tandem across multiple nematode species, where they encode a highly similar peptide; (ii) flp-11 does not appear to be the most widely expressed flp in Caenorhabditis elegans; (iii) in species expressing both flp-11 and flp-32, flp-11 displays a conserved, restricted expression pattern across nematode clades and lifestyles; (iv) in species expressing both flp-11 and flp-32, flp-32 expression is more widespread and less conserved than flp-11; (v) in species expressing only flp-11, the flp-11 expression profile is more similar to the flp-32 profile observed in species expressing both; and (vi) FLP-11 peptides inhibit motor function in multiple nematode species. The biological significance and evolutionary origin of flp-11 and -32 peptide duplication remains unclear despite attempts to identify a common ancestor; this may become clearer as the availability of genomic data improves. This work provides insight into the complexity of the neuropeptidergic system in nematodes, and begins to examine how nematodes may compensate for structural neuronal simplicity. From a parasite control standpoint, this work underscores the importance of basic biological data, and has wider implications for the utility of C. elegans as a model for parasite neurobiology.
Highlights
FMRFamide-like peptides (FLPs) are the largest family of nematode neuropeptides
This study reports the characterisation of FMRFamide-like peptide encoding gene-11 and FMRFamide-like peptide encoding gene-32, two distinct flp genes which encode the analogous peptide, AMRN(A/S)LVRFamide, in multiple nematode species – the only known example of this phenomenon within the FLPergic system of nematodes
In situ hybridisation, immunocytochemistry and behavioural assays we show that: (i) flp-11 and -32 are distinct flp genes expressed individually or in tandem across multiple nematode species, where they encode a highly similar peptide; (ii) flp-11 does not appear to be the most widely expressed flp in Caenorhabditis elegans; (iii) in species expressing both flp-11 and flp-32, flp-11 displays a conserved, restricted expression pattern across nematode clades and lifestyles; (iv) in species expressing both flp-11 and flp-32, flp-32 expression is more widespread and less conserved than flp-11; (v) in species expressing only flp-11, the flp-11 expression profile is more similar to the flp-32 profile observed in species expressing both; and (vi) FLP-11 peptides inhibit motor function in multiple nematode species
Summary
FMRFamide-like peptides (FLPs) are the largest family of nematode neuropeptides. Current genomic data indicate the presence of 32 flp genes encoding >70 RFamide-like peptides (McCoy et al, 2014). Localisation studies for multiple flp genes in several nematode species reveal both positional similarities and differences in orthologous flp gene expression (Kimber et al, 2002; Yew et al, 2007; Jarecki et al, 2010, 2013; Marks and Maule, 2010; Sithigorngul et al, 2011), fuelling speculation that species-specific flpexpression patterns could be linked to behavioural traits that correspond with different habitats and/or life histories While this may be the case, these localisation data were generated exclusively from single nematode species and directly compared with data generated for different species using alternative localisation techniques. The data presented here provide insight into the complexities of the neuropeptidergic system in nematodes, highlighting genuine similarities and differences in flp expression patterns across nematode species that are derived from technique-matched experiments, and appear to be gene-dependent These data encourage the hypothesis that diversity in nematode behaviour and life history is partly supported by plasticity within their highly conserved neuropeptide systems. The findings underscore the importance of both breadth and depth in comparative analyses of nematode neuropeptide signalling systems and have wider implications for the utility of C. elegans as a model for parasite neurobiology and drug target discovery
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