Referenced in: none

Automatically associated channels: SK2

Title: UBE3A Regulates Synaptic Plasticity and Learning and Memory by Controlling SK2 Channel Endocytosis.

Authors: Jiandong Sun, GuoQi Zhu, Yan Liu, Steve Standley, Angela Ji, Rashmi Tunuguntla, Yubin Wang, Chad Claus, Yun Luo, Michel Baudry, Xiaoning Bi

Journal, date & volume: Cell Rep, 2015 Jul 21 , 12, 449-61

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26166566

Abstract
Gated solely by activity-induced changes in intracellular calcium, small-conductance potassium channels (SKs) are critical for a variety of functions in the CNS, from learning and memory to rhythmic activity and sleep. While there is a wealth of information on SK2 gating, kinetics, and Ca(2+) sensitivity, little is known regarding the regulation of SK2 subcellular localization. We report here that synaptic SK2 levels are regulated by the E3 ubiquitin ligase UBE3A, whose deficiency results in Angelman syndrome and overexpression in increased risk of autistic spectrum disorder. UBE3A directly ubiquitinates SK2 in the C-terminal domain, which facilitates endocytosis. In UBE3A-deficient mice, increased postsynaptic SK2 levels result in decreased NMDA receptor activation, thereby impairing hippocampal long-term synaptic plasticity. Impairments in both synaptic plasticity and fear conditioning memory in UBE3A-deficient mice are significantly ameliorated by blocking SK2. These results elucidate a mechanism by which UBE3A directly influences cognitive function.