Bidirectional Regulation of Dendritic Voltage-Gated Potassium Channels by the Fragile X Mental Retardation Protein
Copyright policy )Bidirectional Regulation of Dendritic Voltage-Gated Potassium Channels by the Fragile X Mental Retardation Protein
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.
- Stanford University - Stanford GSB Finland
- University of California, San Francisco United States
- University of California System United States
- Stanford University
- Stanford University United States
Mice, Inbred C57BL, Mice, Knockout, Fragile X Mental Retardation Protein, Mice, HEK293 Cells, Shal Potassium Channels, Potassium Channels, Voltage-Gated, Neuroscience(all), Long-Term Potentiation, Animals, Humans, Dendrites, Cells, Cultured
Mice, Inbred C57BL, Mice, Knockout, Fragile X Mental Retardation Protein, Mice, HEK293 Cells, Shal Potassium Channels, Potassium Channels, Voltage-Gated, Neuroscience(all), Long-Term Potentiation, Animals, Humans, Dendrites, Cells, Cultured
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