Skip to Main content Skip to Navigation
Journal articles

Functional Characterization of a Novel Class of Morantel-Sensitive Acetylcholine Receptors in Nematodes

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.
Document type :
Journal articles
Complete list of metadata

Cited literature [93 references]  Display  Hide  Download

https://hal.archives-ouvertes.fr/hal-01276721
Contributor : Archive Ouverte Prodinra <>
Submitted on : Friday, February 19, 2016 - 8:17:30 PM
Last modification on : Thursday, May 6, 2021 - 2:21:36 PM
Long-term archiving on: : Sunday, November 13, 2016 - 12:05:20 AM

File

Neveu_Courtot_Plos_Pathogens_2...
Publication funded by an institution

Identifiers

Collections

Citation

Elise Courtot, Claude Charvet, Robin Beech, Abdallah Harmache, Adrian J Wolstenholme, et al.. Functional Characterization of a Novel Class of Morantel-Sensitive Acetylcholine Receptors in Nematodes. PLoS Pathogens, Public Library of Science, 2015, 11 (12), pp.e1005267. ⟨10.1371/journal.ppat.1005267⟩. ⟨hal-01276721⟩

Share

Metrics

Record views

270

Files downloads

249