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Published on: January 23, 2018
SUMOylation regulates Kv2.1 and modulates pancreatic beta-cell excitability
Xiao-Qing Dai1, Jelena Kolic, Paolo Marchi
1Department of Pharmacology, University of Alberta, Edmonton, Alberta, T6G 2E1 Canada.
Journal of Cell Science
|February 19, 2009
Summary
Small ubiquitin-like modifier (SUMO) protein attachment inhibits the Kv2.1 potassium channel, a key regulator of pancreatic beta-cell function. This SUMOylation impacts insulin secretion by altering cellular excitability.
Area of Science:
- Molecular Biology
- Cell Physiology
- Endocrinology
Background:
- Small ubiquitin-like modifier (SUMO) proteins regulate diverse cellular processes, including protein localization and function.
- SUMOylation's role in modulating ion channel activity is an emerging area of research.
- The voltage-dependent potassium channel Kv2.1 is critical for regulating pancreatic beta-cell excitability and insulin secretion.
Purpose of the Study:
- To investigate the impact of SUMOylation on the function of the Kv2.1 channel.
- To determine how SUMOylation affects native Kv currents and cellular excitability in pancreatic beta-cells.
Main Methods:
- Co-immunoprecipitation assays to detect Kv2.1 and SUMO1 interaction.
- Electrophysiological recordings (whole-cell patch-clamp) to measure Kv2.1 currents in cell lines and native beta-cells.
- Manipulation of SUMOylation levels using recombinant SUMO1, SUMO1-YFP, Ubc9, and SENP1.
Main Results:
- SUMO1-YFP co-immunoprecipitated with Kv2.1 in HEK 293 cells.
- Recombinant SUMO1 and SUMO1-YFP significantly inhibited cloned Kv2.1 currents.
- SUMO1-YFP expression reduced native Kv currents in human beta-cells and insulinoma cells.
- SUMOylation accelerated Kv2.1 inactivation and slowed recovery from inactivation, widening action potentials and decreasing firing frequency.
- Ubc9 augmented SUMOylation effects, while SENP1 rescued channel function.
Conclusions:
- Protein SUMOylation exerts a potent inhibitory effect on the Kv2.1 channel.
- SUMOylation of Kv2.1 regulates pancreatic beta-cell excitability and insulin secretion.
- Targeting SUMOylation pathways may offer novel therapeutic strategies for diabetes.
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