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.
authors.affiliation: Howard Hughes Medical Institute Departments of Physiology, Biochemistry, and Biophysics, University of California, San Francisco, CA 94158, USA.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Woo-Ping
authors.initials: WP
authors.lastname: Ge
authors.forename: Wendy
authors.initials: W
authors.lastname: Huang
authors.forename: Ye
authors.initials: Y
authors.lastname: He
authors.forename: Gordon X
authors.initials: GX
authors.lastname: Wang
authors.forename: Ashley
authors.initials: A
authors.lastname: Rowson-Baldwin
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Smith
authors.forename: Yuh Nung
authors.initials: YN
authors.lastname: Jan
authors.forename: Lily Yeh
authors.initials: LY
authors.lastname: Jan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology; D051672:Shal Potassium Channels / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D024642:Potassium Channels, Voltage-Gated; D051672:Shal Potassium Channels; C497684:Fmr1 protein, mouse
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