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.

• 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: Neuron (Neuron) Vol. 72 Issue 4 Pg. 630-42 (Nov 17 2011) ISSN: 1097-4199 [Electronic] United States
• PMID: 22099464 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Fmr1 protein, mouse
• Potassium Channels, Voltage-Gated
• Shal Potassium Channels
• Fragile X Mental Retardation Protein

Topics

• Animals
• Cells, Cultured
• Dendrites (physiology)
• Fragile X Mental Retardation Protein (physiology)
• HEK293 Cells
• Humans
• Long-Term Potentiation (physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Potassium Channels, Voltage-Gated (physiology)
• Shal Potassium Channels (antagonists & inhibitors, physiology)