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Neuron. 2011 Nov 17;72(4):630-42. doi: 10.1016/j.neuron.2011.09.033.

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

Author information

  • 1Howard Hughes Medical Institute Departments of Physiology, Biochemistry, and Biophysics, University of California, San Francisco, CA 94158, USA.

Erratum in

  • Neuron. 2011 Dec 22;72(6):1091.

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.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
22099464
[PubMed - indexed for MEDLINE]
PMCID:
PMC3433402
Free PMC Article

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