Functional investigation of muscle acetylcholine receptors from parasitic nematodes

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Neveu, Cédric | Courtot, Elise | Harmache, Abdallah | Blanchard, Alexandra | Guégnard, Fabrice | Beech, Robin N. | Peineau, Nicolas | Wolstenholme, Adrian J. | Castagnone-Sereno, Philippe | Holden-Dye, Lindy | Woods, Debra J. | Charvet, Claude

Edité par CCSD -

International audience. Acetylcholine receptors (AChRs) represent major targets for anti-nematodal drugs including widely used anthelmintics such as levamisole as well as more recent molecules such as monepantel and derquantel. AChRs are made of 5 subunits that are designated as α or non-α based on the presence of a cysteine doublet in their amino-acid sequence. Identical α subunits have the ability to associate together to create functional receptors (homopentamers) whereas non-α subunits have to associate with α subunits in order to generate functional receptors (heteropentamers). Even though nematodes possess a large diversity of AChR subunits, a very small number of AChRs have been characterized so far. In the present study, we have focused our attention on muscle AChR subtypes from animal and plant parasitic nematodes. Using complementary functional approaches including expression in heterologous systems (Xenopus oocytes and C. elegans) and RNAi, we highlighted subunit composition as well as pharmacological properties specific to parasitic nematode species.

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