@article{107ae06072b1417a89b87cc62ab4d02f,
title = "Bidirectional regulation of dendritic voltage-gated potassium channels by the fragile X mental retardation protein",
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.",
author = "Lee, {Hye Young} and Ge, {Woo Ping} and Wendy Huang and Ye He and Wang, {Gordon X.} and Ashley Rowson-Baldwin and Smith, {Stephen J.} and Jan, {Yuh Nung} and Jan, {Lily Yeh}",
note = "Funding Information: We thank Drs. Tom Schwarz and Jeanne M. Nerbonne for kindly providing Kv4.2 KO mice, Dr. Lynn Regan for kindly providing mouse full-length FMRP construct, Dr. Stephanie Ceman for kindly providing GFP-FMRP constructs, Dr. Marc I. Diamond for kindly providing pcDNA3-mouse H1d construct, Dr. Seung Key Jang for sharing MS2-GFP-NLS and MS2BS(6X) constructs, and Dr. Philippe Mourrain and Gemini Skariah for the help and support they provided for the in situ hybridization procedure. We also thank Denan Wang for maintaining mouse lines, Marena Tynan-La Fontaine for genotyping, Dr. Sila Konur for help with imaging and for critical reading of the manuscript and Dr. Desiree Thayer for critical reading of the manuscript and many helpful discussions. This work was supported by the National Institute of Mental Health (L.Y.J.). Y.N.J. and L.Y.J. are investigators of the Howard Hughes Medical Institute. ",
year = "2011",
month = nov,
day = "17",
doi = "10.1016/j.neuron.2011.09.033",
language = "English (US)",
volume = "72",
pages = "630--642",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "4",
}