title: Identification of novel splice variants of the voltage- and Ca²⁺-dependent K⁺-channel SLO-1 of Trichuris muris.
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.
authors.affiliation: Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany.
authors.forename: Esra
authors.initials: E
authors.lastname: Yilmaz
authors.affiliation: Global Drug Discovery - Animal Health - Parasiticides, Bayer HealthCare, 51368 Leverkusen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kulke
authors.affiliation: Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: von Samson-Himmelstjerna
authors.affiliation: Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany. Electronic address: juergen.kruecken@fu-berlin.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Krücken
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D015801:Helminth Proteins / Q000235:genetics*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics*; D012326:RNA Splicing; D014258:Trichuris / Q000235:genetics*
chemical_list: D015801:Helminth Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels
keywords: Alternative splicing; Cyclooctadepsipeptides; Emodepside; Slo-1