ArticlePLoS pathogens2013
Molecular cloning and characterization of novel glutamate-gated chloride channel subunits from Schistosoma mansoni.
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 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- A comparative parasitological, histopathological, and proteomic analysis ofFrontiers in veterinary science · 2025Article
- Prevalence and species identification of trematode metacercariae in Qiqihar, Northeast China.Frontiers in microbiology · 2024Article
- A new family of glutamate-gated chloride channels in parasitic sea louse Caligus rogercresseyi: A subunit refractory to activation by ivermectin is dominant in heteromeric assemblies.PLoS pathogens · 2023Article
- Phenotypic Profiling of Macrocyclic Lactones on ParasiticAntimicrobial agents and chemotherapy · 2023Article
- Schistosomes contain divergent ligand-gated ion channels with an atypical Cys-loop motif.microPublication biology · 2023Article
- Mitochondria as a Potential Target for the Development of Prophylactic and Therapeutic Drugs against Schistosoma mansoni Infection.Antimicrobial agents and chemotherapy · 2021Article
- The effect of ivermectin alone and in combination with cobicistat or elacridar in experimental Schistosoma mansoni infection in mice.Scientific reports · 2021Article
- Non-sedating benzodiazepines cause paralysis and tissue damage in the parasitic blood fluke Schistosoma mansoni.PLoS neglected tropical diseases · 2019Article
- Identification and characterization of sodium and chloride-dependent gamma-aminobutyric acid (GABA) transporters from eukaryotic pathogens as a potential drug target.Bioinformation · 2018Article
- A high-throughput colorimetric assay for detection of Schistosoma mansoni viability based on the tetrazolium salt XTT.Parasites & vectors · 2017Article
- Trapping of ivermectin by a pentameric ligand-gated ion channel upon open-to-closed isomerization.Scientific reports · 2017Article
- Mutational Analysis at Intersubunit Interfaces of an Anionic Glutamate Receptor Reveals a Key Interaction Important for Channel Gating by Ivermectin.Frontiers in molecular neuroscience · 2017Article
- Recent Duplication and Functional Divergence in Parasitic Nematode Levamisole-Sensitive Acetylcholine Receptors.PLoS neglected tropical diseases · 2016Article
- Pipeline for the identification and classification of ion channels in parasitic flatworms.Parasites & vectors · 2016Article
- Article
- Molecular basis for convergent evolution of glutamate recognition by pentameric ligand-gated ion channels.Scientific reports · 2015Article
- Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms.PLoS neglected tropical diseases · 2015Article
- Schistosome ABC multidrug transporters: From pharmacology to physiology.International journal for parasitology. Drugs and drug resistance · 2014Review
- Ion channels and drug transporters as targets for anthelmintics.Current clinical microbiology reports · 2014Article
- Characterization of the Ca2+-gated and voltage-dependent K+-channel Slo-1 of nematodes and its interaction with emodepside.PLoS neglected tropical diseases · 2014Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cys-loop ligand-gated ion channels (LGICs) mediate fast ionotropic neurotransmission. They are proven drug targets in nematodes and arthropods, but are poorly characterized in flatworms. In this study, we characterized the anion-selective, non-acetylcholine-gated Cys-loop LGICs from Schistosoma mansoni. Full-length cDNAs were obtained for SmGluCl-1 (Smp_096480), SmGluCl-2 (Smp_015630) and SmGluCl-3 (Smp_104890). A partial cDNA was retrieved for SmGluCl-4 (Smp_099500/Smp_176730). Phylogenetic analyses suggest that SmGluCl-1, SmGluCl-2, SmGluCl-3 and SmGluCl-4 belong to a novel clade of flatworm glutamate-gated chloride channels (GluCl) that includes putative genes from trematodes and cestodes. The flatworm GluCl clade was distinct from the nematode-arthropod and mollusc GluCl clades, and from all GABA receptors. We found no evidence of GABA receptors in S. mansoni. SmGluCl-1, SmGluCl-2 and SmGluCl-3 subunits were characterized by two-electrode voltage clamp (TEVC) in Xenopus oocytes, and shown to encode Cl⁻-permeable channels gated by glutamate. SmGluCl-2 and SmGluCl-3 produced functional homomers, while SmGluCl-1 formed heteromers with SmGluCl-2. Concentration-response relationships revealed that the sensitivity of SmGluCl receptors to L-glutamate is among the highest reported for GluCl receptors, with EC₅₀ values of 7-26 µM. Chloride selectivity was confirmed by current-voltage (I/V) relationships. SmGluCl receptors are insensitive to 1 µM ivermectin (IVM), indicating that they do not belong to the highly IVM-sensitive GluClα subtype group. SmGluCl receptors are also insensitive to 10 µM meclonazepam, a schistosomicidal benzodiazepine. These results provide the first molecular evidence showing the contribution of GluCl receptors to L-glutamate signaling in S. mansoni, an unprecedented finding in parasitic flatworms. Further work is needed to elucidate the roles of GluCl receptors in schistosomes and to explore their potential as drug targets.
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