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XB-ART-53998
Acta Physiol (Oxf). September 9, 2017;

SUMO co-expression modifies KV 11.1 channel activity.

Steffensen AB , Andersen MN , Mutsaers N , Mujezinovic A , Schmitt N .


Abstract
The voltage-gated potassium channel KV 11.1 is the molecular basis for the IKr current which plays an important role in cardiac physiology. Its malfunction is associated with both inherited and acquired cardiac arrhythmias. Native currents differ from those in experimental models, suggesting additional regulatory mechanisms. We hypothesised that the post-translational modification sumoylation finetunes channel activity. The functional effects of sumoylation on KV 11.1 were addressed by employing two-electrode voltage-clamp (TEVC) experiments in Xenopus laevis oocytes. Site-directed mutagenesis enabled a further analyse of the SUMO-target amino acids. We assessed protein expression levels and used confocal imaging for localization studies. Co-expression with Ubc9 and SUMO alters the electrophysiological properties of KV 11.1 leading to a decrease in steady-state current amplitude largely due to faster inactivation and alteration of deactivation kinetics. We identified three lysines (K21, K93, and K116) in the PAS-domain as the putative SUMO-targets. This study indicates KV 11.1 as a sumoylation target, and offers the three main targets; K21, K93, and K116. Furthermore, it proposes an underlying mechanism for the observed kinetic impact of the PAS domain. This article is protected by copyright. All rights reserved.

PubMed ID: 28888063
Article link: Acta Physiol (Oxf).



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