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.

journal_name

Mol Biochem Parasitol

authors

Yilmaz E,Kulke D,von Samson-Himmelstjerna G,Krücken J

doi

10.1016/j.molbiopara.2015.03.001

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

5-8

issue

1-2

eissn

0166-6851

issn

1872-9428

pii

S0166-6851(15)00011-0

journal_volume

199

pub_type

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