ArticlePLoS pathogens2013
acr-23 Encodes a monepantel-sensitive channel in Caenorhabditis elegans.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 50 citations in OpenAlex.
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- Structural insights into the molecular effects of the anthelmintics monepantel and betaine on the Caenorhabditis elegans acetylcholine receptor ACR-23.The EMBO journal · 2024Article
- Unveiling the crucial role of betaine: modulation of GABA homeostasis via SLC6A1 transporter (GAT1).Cellular and molecular life sciences : CMLS · 2024Article
- The diverse family of Cys-loop receptors inBiophysical reviews · 2023Review
- Induction of endoplasmic reticulum stress is associated with the anti-tumor activity of monepantel across cancer types.Cancer medicine · 2023Article
- Neuronally produced betaine acts via a ligand-gated ion channel to control behavioral states.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Reconstitution of an N-AChR from Brugia malayi, an evolved change in acetylcholine receptor accessory protein requirements in filarial parasites.PLoS pathogens · 2022Article
- The nematode serotonin-gated chloride channel MOD-1: A novel target for anthelmintic therapy.The Journal of biological chemistry · 2022Article
- TheMolecules (Basel, Switzerland) · 2022Article
- Complementary Approaches with Free-living and Parasitic Nematodes to Understanding Anthelmintic Resistance.Trends in parasitology · 2021Review
- Natural Compounds from the Marine Brown AlgaPathogens (Basel, Switzerland) · 2020Article
- Genotypic characterisation of monepantel resistance in historical and newly derived field strains of Teladorsagia circumcincta.International journal for parasitology. Drugs and drug resistance · 2019Article
- Diisopropylphenyl-imidazole (DII): A new compound that exerts anthelmintic activity through novel molecular mechanisms.PLoS neglected tropical diseases · 2018Article
- Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing.Scientific reports · 2018Article
- A BRIEF REVIEW ON THE MODE OF ACTION OF ANTINEMATODAL DRUGS.Acta veterinaria · 2017Article
- Recent Duplication and Functional Divergence in Parasitic Nematode Levamisole-Sensitive Acetylcholine Receptors.PLoS neglected tropical diseases · 2016Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Monepantel is a member of the recently identified class of anthelmintics known as the amino-acetonitrile derivatives (AADs). Monepantel controls all major gastro-intestinal nematodes in sheep including those that are resistant to the classical anthelmintics. Previous studies have shown that the Caenorhabditis elegans acr-23 and the Haemonchus contortus Hco-mptl-1 genes may be prominent targets of monepantel. With this discovery it became possible to investigate the mode of action of monepantel in nematodes at the molecular level. In the present study, we show that a C. elegans mutant acr-23 strain is fully rescued by expressing the wild-type acr-23 gene. Moreover, we present a new mutant allele, and characterize acr-23 alleles genetically. We also show that acr-23 is expressed in body wall muscle cells, and provide therefore a possible explanation for the paralysis caused by monepantel. Furthermore, genetic evidence suggests that the chaperone RIC-3 is required for expression of full monepantel resistance. Finally, we present reconstitution of the C. elegans ACR-23 receptor in Xenopus laevis oocytes and provide direct evidence of its modulation by monepantel. Conversely, co-injection of the chaperone RIC-3 had no impact for channel reconstitution in X. laevis oocytes. These results reinforce the involvement of the ACR-23 family in the mode of action of monepantel and advance our understanding of this new class of anthelmintics.
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