RRC ID 53485
著者 Courtot E, Charvet CL, Beech RN, Harmache A, Wolstenholme AJ, Holden-Dye L, O'Connor V, Peineau N, Woods DJ, Neveu C.
タイトル Functional Characterization of a Novel Class of Morantel-Sensitive Acetylcholine Receptors in Nematodes.
ジャーナル PLoS Pathog
Abstract Acetylcholine receptors are pentameric ligand-gated channels involved in excitatory neuro-transmission in both vertebrates and invertebrates. In nematodes, they represent major targets for cholinergic agonist or antagonist anthelmintic drugs. Despite the large diversity of acetylcholine-receptor subunit genes present in nematodes, only a few receptor subtypes have been characterized so far. Interestingly, parasitic nematodes affecting human or animal health possess two closely related members of this gene family, acr-26 and acr-27 that are essentially absent in free-living or plant parasitic species. Using the pathogenic parasitic nematode of ruminants, Haemonchus contortus, as a model, we found that Hco-ACR-26 and Hco-ACR-27 are co-expressed in body muscle cells. We demonstrated that co-expression of Hco-ACR-26 and Hco-ACR-27 in Xenopus laevis oocytes led to the functional expression of an acetylcholine-receptor highly sensitive to the anthelmintics morantel and pyrantel. Importantly we also reported that ACR-26 and ACR-27, from the distantly related parasitic nematode of horses, Parascaris equorum, also formed a functional acetylcholine-receptor highly sensitive to these two drugs. In Caenorhabditis elegans, a free-living model nematode, we demonstrated that heterologous expression of the H. contortus and P. equorum receptors drastically increased its sensitivity to morantel and pyrantel, mirroring the pharmacological properties observed in Xenopus oocytes. Our results are the first to describe significant molecular determinants of a novel class of nematode body wall muscle AChR.
巻・号 11(12)
ページ e1005267
公開日 2015-12-1
DOI 10.1371/journal.ppat.1005267
PII PPATHOGENS-D-15-01170
PMID 26625142
PMC PMC4666645
MeSH Animals Anthelmintics / pharmacology Ascaridoidea / genetics Ascaridoidea / metabolism Base Sequence Haemonchus / genetics Haemonchus / metabolism Helminth Proteins / genetics Helminth Proteins / metabolism* In Situ Hybridization Molecular Sequence Data Morantel / pharmacology Nematoda / genetics Nematoda / metabolism* Patch-Clamp Techniques Phylogeny Polymerase Chain Reaction Receptors, Cholinergic / genetics Receptors, Cholinergic / metabolism*
IF 6.463
引用数 12
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