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SUMMARY:Dendritic Potassium Channel Regulation by Fragile X Mental Retarda
 tion Protein (FMRP) - Dr HyeYoung Lee\, Howard Hughes Medical Institute\, 
 University of California in San Francisco
DTSTART:20140123T160000Z
DTEND:20140123T170000Z
UID:TALK49727@talks.cam.ac.uk
CONTACT:Philipe Mendonca
DESCRIPTION:Fragile X syndrome (FXS) is a common form of mental disability
  and one of the known causes of autism. The mutation responsible for FXS i
 s a large expansion of the trinucleotide CGG repeats that leads to DNA met
 hylation of the fragile X mental retardation gene 1 (FMR1) and transcripti
 onal silencing\, resulting in the absence of fragile X mental retardation 
 protein (FMRP)\, an mRNA binding protein. Although it is widely known that
  FMRP is critical for metabotropic glutamate receptor (mGluR)-­‐ depend
 ent long-­‐term depression (LTD)\, which has provided a general theme f
 or developing pharmacological drugs for FXS\, specific downstream targets 
 of FMRP may also be of therapeutic value. Since alterations in potassium c
 hannel expression level or activity could underlie neuronal network defect
 s in FXS\, we will describe our recent findings on how the dendritic potas
 sium channel\, Kv4.2 might be altered in mouse models of FXS and the possi
 ble therapeutic avenues for treating FXS. How transmitter receptors modula
 te neuronal signaling by regulating voltage-­‐gated ion channel express
 ion remains an open question. Recently we reported dendritic localization 
 of mRNA of Kv4.2 voltage-­‐gated potassium channel\, which regulates sy
 naptic plasticity\, and its local translational regulation by FMRP. FMRP s
 uppression 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 bi
 nds FMRP. Moreover\, treating hippocampal slices from fmr1 KO mice with Kv
 4 channel blocker restores long-­‐term potentiation (LTP) induced by mo
 derate stimuli. The evaluation of Kv4.2 potassium channels as potential th
 erapeutic targets for FXS will allow us to be extended to include addition
 al proof-­‐of-­‐principle tests for genetic reduction of Kv4.2 as po
 tential ways to reduce fmr1 KO mutant phenotypes\, with a strong interest 
 in pursuing translational research to develop treatments and improve outco
 mes for individuals with FXS.
LOCATION:Hodgkin Huxley Seminar Room\, Physiology Building\, Downing Site
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