Identification of novel splice variants of the voltage- and Ca²⁺-dependent K⁺-channel SLO-1 of Trichuris muris

Molecular and Biochemical Parasitology
Esra YilmazJürgen Krücken

Abstract

The anthelmintic cyclooctadepsipeptide emodepside is effective against nematodes showing resistance against established drug classes. Emodepside exerts its nematicidal effects mainly through its validated target, the tetrameric voltage- and calcium-activated potassium channel SLO-1. Two slo-1 genes were described in Trichuris muris. Alternative splicing is known to alter SLO-1 properties. Here, 16 T. muris splice variants for slo-1.1 and three variants for slo-1.2 were identified in addition to previously described variants. Splice variants caused by intron retentions and/or exon exclusions encode varyingly truncated subunits. Depending on the subunit composition, channels might have altered physiological and pharmacological properties including different modulation by calcium and/or voltage or reduced emodepside susceptibility which might lead to emodepside resistance as observed in Caenorhabditis elegans expressing only similarly truncated Slo-1. The comprehensive characterisation of splice variants is a prerequisite for functional analysis and confirmed conservation of remarkable differences found between both slo-1 paralogs in Trichuris suis.

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Citations

Nov 30, 2020·International Journal for Parasitology. Drugs and Drug Resistance·Steffen R HahnelDaniel Kulke

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