SUMO co-expression modifies KV 11.1 channel activity

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SUMO co-expression modifies KV 11.1 channel activity. / Steffensen, Annette Buur; Andersen, Martin Nybo; Mutsaers, Nancy; Mujezinovic, Amer; Schmitt, Nicole.

In: Acta Physiologica (Print), Vol. 222, No. 3, e12974, 03.2018.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Steffensen, AB, Andersen, MN, Mutsaers, N, Mujezinovic, A & Schmitt, N 2018, 'SUMO co-expression modifies KV 11.1 channel activity', Acta Physiologica (Print), vol. 222, no. 3, e12974. https://doi.org/10.1111/apha.12974

APA

Steffensen, A. B., Andersen, M. N., Mutsaers, N., Mujezinovic, A., & Schmitt, N. (2018). SUMO co-expression modifies KV 11.1 channel activity. Acta Physiologica (Print), 222(3), [e12974]. https://doi.org/10.1111/apha.12974

Vancouver

Steffensen AB, Andersen MN, Mutsaers N, Mujezinovic A, Schmitt N. SUMO co-expression modifies KV 11.1 channel activity. Acta Physiologica (Print). 2018 Mar;222(3). e12974. https://doi.org/10.1111/apha.12974

Author

Steffensen, Annette Buur ; Andersen, Martin Nybo ; Mutsaers, Nancy ; Mujezinovic, Amer ; Schmitt, Nicole. / SUMO co-expression modifies KV 11.1 channel activity. In: Acta Physiologica (Print). 2018 ; Vol. 222, No. 3.

Bibtex

@article{3a37f3d84631473397aaaf4dc8ce9d47,
title = "SUMO co-expression modifies KV 11.1 channel activity",
abstract = "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.",
keywords = "Journal Article",
author = "Steffensen, {Annette Buur} and Andersen, {Martin Nybo} and Nancy Mutsaers and Amer Mujezinovic and Nicole Schmitt",
note = "This article is protected by copyright. All rights reserved.",
year = "2018",
month = "3",
doi = "10.1111/apha.12974",
language = "English",
volume = "222",
journal = "Acta Physiologica (Print)",
issn = "1748-1708",
publisher = "Wiley-Blackwell",
number = "3",

}

RIS

TY - JOUR

T1 - SUMO co-expression modifies KV 11.1 channel activity

AU - Steffensen, Annette Buur

AU - Andersen, Martin Nybo

AU - Mutsaers, Nancy

AU - Mujezinovic, Amer

AU - Schmitt, Nicole

N1 - This article is protected by copyright. All rights reserved.

PY - 2018/3

Y1 - 2018/3

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1111/apha.12974

DO - 10.1111/apha.12974

M3 - Journal article

C2 - 28888063

VL - 222

JO - Acta Physiologica (Print)

JF - Acta Physiologica (Print)

SN - 1748-1708

IS - 3

M1 - e12974

ER -

ID: 183762890