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SUMO co‐expression modifies K V 11.1 channel activity
Author(s) -
Steffensen A. B.,
Andersen M. N.,
Mutsaers N.,
Mujezinovic A.,
Schmitt N.
Publication year - 2018
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12974
Subject(s) - sumo protein , xenopus , biophysics , potassium channel , chemistry , mutagenesis , microbiology and biotechnology , patch clamp , electrophysiology , amino acid , mutation , biology , biochemistry , neuroscience , ubiquitin , receptor , gene
Aim The voltage‐gated potassium channel K V 11.1 is the molecular basis for the I K r 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 hypothesized that the post‐translational modification sumoylation fine‐tunes channel activity. Methods The functional effects of sumoylation on K V 11.1 were addressed by employing two‐electrode voltage‐clamp ( TEVC ) experiments in Xenopus laevis oocytes. Site‐directed mutagenesis enabled a further analysis of the SUMO ‐target amino acids. We assessed protein expression levels and used confocal imaging for localization studies. Results Co‐expression with Ubc9 and SUMO alters the electrophysiological properties of K V 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. Conclusion This study indicates K V 11.1 as a sumoylation target and offers three main targets: K21, K93, and K116. Furthermore, it proposes an underlying mechanism for the observed kinetic impact of the PAS domain.