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FMRP(1–297)-tat restores ion channel and synaptic function in a model of Fragile X syndrome

Author

Listed:
  • Xiaoqin Zhan

    (University of Calgary)

  • Hadhimulya Asmara

    (University of Calgary)

  • Ning Cheng

    (University of Calgary)

  • Giriraj Sahu

    (University of Calgary)

  • Eduardo Sanchez

    (University of Calgary)

  • Fang-Xiong Zhang

    (University of Calgary)

  • Gerald W. Zamponi

    (University of Calgary
    University of Calgary)

  • Jong M. Rho

    (University of Calgary
    University of Calgary)

  • Ray W. Turner

    (University of Calgary)

Abstract

Fragile X Syndrome results from a loss of Fragile X Mental Retardation Protein (FMRP). We now show that FMRP is a member of a Cav3-Kv4 ion channel complex that is known to regulate A-type potassium current in cerebellar granule cells to produce mossy fiber LTP. Mossy fiber LTP is absent in Fmr1 knockout (KO) mice but is restored by FMRP(1-297)-tat peptide. This peptide further rapidly permeates the blood-brain barrier to enter cells across the cerebellar-cortical axis that restores the balance of protein translation for at least 24 h and transiently reduces elevated levels of activity of adult Fmr1 KO mice in the Open Field Test. These data reveal that FMRP(1-297)-tat can improve function from the levels of protein translation to synaptic efficacy and behaviour in a model of Fragile X syndrome, identifying a potential therapeutic strategy for this genetic disorder.

Suggested Citation

  • Xiaoqin Zhan & Hadhimulya Asmara & Ning Cheng & Giriraj Sahu & Eduardo Sanchez & Fang-Xiong Zhang & Gerald W. Zamponi & Jong M. Rho & Ray W. Turner, 2020. "FMRP(1–297)-tat restores ion channel and synaptic function in a model of Fragile X syndrome," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16250-4
    DOI: 10.1038/s41467-020-16250-4
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