SUMOylation and Potassium Channels: Links to Epilepsy and Sudden Death.

Neuronal potassium ion channels play an essential role in the generation of the action potential and excitability of neurons. The dysfunction of ion channel subunits can cause channelopathies, which are associated in some cases with sudden unexplained death in epilepsy SUDEP. The physiological roles of neuronal ion channels have been largely determined, but little is known about the molecular mechanisms underlying neurological channelopathies, especially the determinants of the channels' regulation. SUMO (small ubiquitin-like modifier) proteins covalently conjugate lysine residues in a large number of target proteins and modify their functions. SUMO modification (SUMOylation) has emerged as an important regulatory mechanism for protein stability, function, subcellular localization, and protein-protein interactions. Since SUMO was discovered almost 20 years ago, the biological contribution of SUMOylation has not fully understood. It is until recently that the physiological impacts of SUMOylation on the regulation of neuronal potassium ion channels have been investigated. It is well established that SUMOylation controls many aspects of nuclear function, but it is now clear that it is also a key determinant in the function of potassium channels, and SUMOylation has also been implicated in a wide range of channelopathies, including epilepsy and sudden death.