Nematode neuropeptide receptors and their development as anthelmintic screens

Greenwood, Karen G.; Williams, Tracey; Geary, Timothy G.

doi:10.1017/s003118200500819x

Cited by 27 publications

(22 citation statements)

References 73 publications

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“…In addition, FLP-18 peptides were also identified as ligands of the receptors NPR-4 and NPR-10 (40, 62). An unusual structure-activity relationship has been suggested for the C. elegans receptor FRPR-3 (47, 50). Ligands identified for this GPCR include a FLP-7 (TPMQRSSMVRFamide) and FLP-11 (AMRNALVRFamide) peptide, whereas structurally similar peptides encoded on the same precursor proteins were ineffective at activating the receptor (50).…”

Section: Flp-receptors In Nematodesmentioning

confidence: 99%

The FMRFamide-Like Peptide Family in Nematodes

et al. 2014

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In the three decades since the FMRFamide peptide was isolated from the mollusk Macrocallista nimbosa, structurally similar peptides sharing a C-terminal RFamide motif have been identified across the animal kingdom. FMRFamide-like peptides (FLPs) represent the largest known family of neuropeptides in invertebrates. In the phylum Nematoda, at least 32 flp-genes are classified, making the FLP system of nematodes unusually complex. The diversity of the nematode FLP complement is most extensively mapped in Caenorhabditis elegans, where over 70 FLPs have been predicted. FLPs have shown to be expressed in the majority of the 302 C. elegans neurons including interneurons, sensory neurons, and motor neurons. The vast expression of FLPs is reflected in the broad functional repertoire of nematode FLP signaling, including neuroendocrine and neuromodulatory effects on locomotory activity, reproduction, feeding, and behavior. In contrast to the many identified nematode FLPs, only few peptides have been assigned a receptor and there is the need to clarify the pathway components and working mechanisms of the FLP signaling network. Here, we review the diversity, distribution, and functions of FLPs in nematodes.

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Section: Flp-receptors In Nematodesmentioning

confidence: 99%

The FMRFamide-Like Peptide Family in Nematodes

et al. 2014

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“…The potential areas for investigations of the neurobiology of plant-parasitic nematodes are too broad to expand on here, but one which relates to our ongoing efforts is worth noting. Significant progress has been made in recent years in the discovery and functional expression of FLP receptors in C. elegans (for reviews see Greenwood et al, 2005;McVeigh et al, 2006). These efforts have relied on the heterologous expression of putative neuropeptide receptors (these are designated 'orphans' because the endogenous activating ligands are unknown) and the subsequent testing of neuropeptides for their ability to activate each receptor.…”

Section: Interrogation Of Neuronal Functionmentioning

confidence: 99%

Getting to the root of neuronal signalling in plant-parasitic nematodes using RNA interference

Fleming

McKinney

McMaster

et al. 2007

Nematol

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A variety of genes expressed in preparasitic second-stage juveniles (J2) of plant-parasitic nematodes appear to be vulnerable to RNA interference (RNAi) in vitro by coupling double-stranded (ds)RNA soaking with the artificial stimulation of pharyngeal pumping. Also, there is mounting evidence that the in planta generation of nematode-specific double-stranded RNAs (dsRNAs) has real utility in the control of these pests. Although neuronally-expressed genes in Caenorhabditis elegans are commonly refractory to RNAi, we have discovered that neuronally-expressed genes in plant-parasitic nematodes are highly susceptible to RNAi and that silencing can be induced by simple soaking procedures without the need for pharyngeal stimulation. Since most front-line anthelmintics that are used for the control of nematode parasites of animals and humans act to disrupt neuromuscular coordination, we argue that intercellular signalling processes associated with neurons have much appeal as targets for transgenic plant-based control strategies for plant-parasitic nematodes. FMRFamide-like peptides (FLPs) are a large family of neuropeptides which are intimately associated with neuromuscular regulation, and our studies on flp gene function in plant-parasitic nematodes have revealed that their expression is central to coordinated locomotory activities. We propose that the high level of conservation in nervous systems across nematodes coupled with the RNAi-susceptibility of neuronally-expressed genes in plant-parasitic nematodes provides a valuable research tool which could be used to interrogate neuronal signalling processes in nematodes.

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“…If that function is found essential for the maintenance of the parasite in the host, the receptor defined highthroughput screens could be established for finding nonpeptidic small molecules, either receptor agonists or antagonists, as potential antiparasitic drug candidates. [6][7][8][9] Despite intense efforts in many laboratories over the last decade, most of the C. elegans neuropeptide G-proteincoupled receptors (GPCRs) remain orphans, as only a few have been matched with their native ligands. [10][11][12][13][14][15][16] Functional expression of C. elegans neuropeptide GPCRs in mammalian expression systems has been challenging and problematic, mainly due to the apparently poor compatibility of mammalian G-proteins and other accessory proteins with heterelogously expressed nematode receptors.…”

Section: Introductionmentioning

confidence: 99%