title: The Brugia malayi neuropeptide receptor-4 is activated by FMRFamide-like peptides and signals via Gαi.
abstract: Genetic studies undertaken in the model organism Caenorhabditis elegans have demonstrated the importance of neuropeptidergic signalling in nematode physiology. Disruption of this signalling may have deleterious phenotypic consequences, including altered locomotion, feeding behaviour, and reproduction. Neuropeptide G protein-coupled receptors (GPCRs) that transduce many of these signals therefore represent cogent drug targets. Recently published genomic sequencing data for a number of parasitic helminths of medical and veterinary importance has revealed the apparent conservation of a number of neuropeptides, and neuropeptide receptors between parasitic and free-living species, raising the intriguing possibility of developing broad-spectrum anthelmintic therapeutics. Here, we identify and clone a neuropeptide receptor, NPR-4, from the human filarial nematode Brugia malayi and demonstrate its activation in vitro, by FMRFamide-like peptides of the FLP-18 family, and intracellular signalling via Gαi mediated pathways. These data represent the first example of deorphanisation of a neuropeptide GPCR in any parasitic helminth species.
authors.affiliation: MRC/UCT Receptor Biology Research Unit, Institute of Infectious Disease and Molecular Medicine and Division of Medical Biochemistry, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925 Cape Town, South Africa.
authors.forename: Ross C
authors.initials: RC
authors.lastname: Anderson
authors.affiliation: MRC/UCT Receptor Biology Research Unit, Institute of Infectious Disease and Molecular Medicine and Division of Medical Biochemistry, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925 Cape Town, South Africa.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Newton
authors.affiliation: MRC/UCT Receptor Biology Research Unit, Institute of Infectious Disease and Molecular Medicine and Division of Medical Biochemistry, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925 Cape Town, South Africa; Mammal Research Institute, Room 2-33 Zoology and Entomology, University of Pretoria, Pretoria 0001, South Africa.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Millar
authors.affiliation: MRC/UCT Receptor Biology Research Unit, Institute of Infectious Disease and Molecular Medicine and Division of Medical Biochemistry, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925 Cape Town, South Africa. Electronic address: arieh.katz@uct.ac.za.
authors.forename: Arieh A
authors.initials: AA
authors.lastname: Katz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017178:Brugia malayi / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans; D005368:Filariasis / Q000378:metabolism* / Q000469:parasitology*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction
chemical_list: D015801:Helminth Proteins; D009479:Neuropeptides; D018013:Receptors, Neuropeptide; D019206:GTP-Binding Protein alpha Subunits, Gi-Go
keywords: Brugia malayi; FMRFamide-like peptides; G protein-coupled receptor; Lymphatic filariasis; Neuropeptide; Neuropeptide receptor