Referenced in: none

Automatically associated channels: Kv1.4 , Kv3.1 , Kv4.2

Title: Bidirectional regulation of dendritic voltage-gated potassium channels by the fragile x mental retardation protein.

Authors: Hye Young Lee, Woo-Ping Ge, Wendy Huang, Ye He, Gordon X Wang, Ashley Rowson-Baldwin, Stephen J Smith, Yuh Nung Jan, Lily Yeh Jan

Journal, date & volume: Neuron, 2011 Nov 17 , 72, 630-42

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22099464

Abstract
How transmitter receptors modulate neuronal signaling by regulating voltage-gated ion channel expression remains an open question. Here we report dendritic localization of mRNA of Kv4.2 voltage-gated potassium channel, which regulates synaptic plasticity, and its local translational regulation by fragile X mental retardation protein (FMRP) linked to fragile X syndrome (FXS), the most common heritable mental retardation. FMRP suppression of Kv4.2 is revealed by elevation of Kv4.2 in neurons from fmr1 knockout (KO) mice and in neurons expressing Kv4.2-3'UTR that binds FMRP. Moreover, treating hippocampal slices from fmr1 KO mice with Kv4 channel blocker restores long-term potentiation induced by moderate stimuli. Surprisingly, recovery of Kv4.2 after N-methyl-D-aspartate receptor (NMDAR)-induced degradation also requires FMRP, likely due to NMDAR-induced FMRP dephosphorylation, which turns off FMRP suppression of Kv4.2. Our study of FMRP regulation of Kv4.2 deepens our knowledge of NMDAR signaling and reveals a FMRP target of potential relevance to FXS.