Bidirectional regulation of dendritic voltage-gated potassium channels by the fragile X mental retardation protein

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

Research output: Contribution to journalArticle

44 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)630-642
Number of pages13
JournalNeuron
Volume72
Issue number4
DOIs
StatePublished - Nov 17 2011

Fingerprint

Fragile X Mental Retardation Protein
Voltage-Gated Potassium Channels
N-Methyl-D-Aspartate Receptors
Fragile X Syndrome
Knockout Mice
Shal Potassium Channels
Neurons
Neuronal Plasticity
Long-Term Potentiation
3' Untranslated Regions
Ion Channels
Intellectual Disability
Messenger RNA

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Bidirectional regulation of dendritic voltage-gated potassium channels by the fragile X mental retardation protein. / Lee, Hye Young; Ge, Woo Ping; Huang, Wendy; He, Ye; Wang, Gordon X.; Rowson-Baldwin, Ashley; Smith, Stephen J.; Jan, Yuh Nung; Jan, Lily Yeh.

In: Neuron, Vol. 72, No. 4, 17.11.2011, p. 630-642.

Research output: Contribution to journalArticle

Lee, HY, Ge, WP, Huang, W, He, Y, Wang, GX, Rowson-Baldwin, A, Smith, SJ, Jan, YN & Jan, LY 2011, 'Bidirectional regulation of dendritic voltage-gated potassium channels by the fragile X mental retardation protein', Neuron, vol. 72, no. 4, pp. 630-642. https://doi.org/10.1016/j.neuron.2011.09.033
Lee, Hye Young ; Ge, Woo Ping ; Huang, Wendy ; He, Ye ; Wang, Gordon X. ; Rowson-Baldwin, Ashley ; Smith, Stephen J. ; Jan, Yuh Nung ; Jan, Lily Yeh. / Bidirectional regulation of dendritic voltage-gated potassium channels by the fragile X mental retardation protein. In: Neuron. 2011 ; Vol. 72, No. 4. pp. 630-642.
@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}",
year = "2011",
month = "11",
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",

}

TY - JOUR

T1 - Bidirectional regulation of dendritic voltage-gated potassium channels by the fragile X mental retardation protein

AU - Lee, Hye Young

AU - Ge, Woo Ping

AU - Huang, Wendy

AU - He, Ye

AU - Wang, Gordon X.

AU - Rowson-Baldwin, Ashley

AU - Smith, Stephen J.

AU - Jan, Yuh Nung

AU - Jan, Lily Yeh

PY - 2011/11/17

Y1 - 2011/11/17

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=81355150782&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=81355150782&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2011.09.033

DO - 10.1016/j.neuron.2011.09.033

M3 - Article

C2 - 22099464

AN - SCOPUS:81355150782

VL - 72

SP - 630

EP - 642

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 4

ER -