Heterologous Expression in Remodeled . : A Platform for Monoaminergic Agonist Identification and Anthelmintic Screening

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Monoamines, such as serotonin (5-HT) and tyramine (TA), paralyze both free-living and parasitic nematodes when applied exogenously. Since nematode cell lines are not available and animal screening options are limited, we have developed a screening platform to identify monoamine receptor agonists that involves the heterologous expression of key receptors from parasitic nematodes in chimeric, genetically-engineered mutant C. elegans, at sites likely to yield robust phenotypes upon agonist stimulation. Specifically, we have demonstrated that agonist dependent activation of Gαo-coupled 5-HT receptors or monoamine-gated Cl- channels in key interneurons, cholinergic motor neurons or body wall muscle inhibited locomotion and caused paralysis. This approach includes nematode-specific accessory proteins and the nematode cuticle, and appears to preserve the unique pharmacologies of the individual receptors. Together these data highlight the utility of these transgenic C. elegans for agonist identification and their potential for anthelmintic screening.

Vyšlo v časopise: Heterologous Expression in Remodeled . : A Platform for Monoaminergic Agonist Identification and Anthelmintic Screening. PLoS Pathog 11(4): e32767. doi:10.1371/journal.ppat.1004794
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004794

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