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RbFox1 up-regulation impairs BDNF-dependent hippocampal LTP by dysregulating TrkB isoform expression levels

  1. Author:
    Tomassoni Ardori,Francesco
    Fulgenzi,Gianluca
    Becker,Jodi
    Barrick,Colleen
    Palko,Mary Ellen
    Kuhn,Skyler
    Koparde,Vishal
    Cam, Maggie
    Yanpallewar,Sudhirkumar
    Oberdoerffer,Shalini
    Tessarollo,Lino [ORCID]

  2. Author Address

    National Cancer Institute, National Institutes of Health, National Cancer Institute, Frederick, United States., Neural Development Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, United States., Collaborative Bioinformatics Resource, National Cancer Institute, National Institutes of Health, Frederick, United States., Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Frederick, United States.,
    1. Year: 2019
    2. Date: Aug 20
    3. Epub Date: 2019 08 20
  2. Journal: eLife
    1. 8
    2. Pages: pii: e49673
  4. Type of Article: Article
  5. Article Number: e49673
  6. ISSN: 2050-084X
  1. Abstract:

    Brain Derived Neurotrophic Factor (BDNF) is a potent modulator of brain synaptic plasticity. Signaling defects caused by dysregulation of its NTrk2 (TrkB) kinase (TrkB.FL) and truncated receptors (TrkB.T1) have been linked to the pathophysiology of several neurological and neurodegenerative disorders. We found that upregulation of Rbfox1, an RNA binding protein associated with intellectual disability, epilepsy and autism, increases selectively hippocampal TrkB.T1 isoform expression. Physiologically, increased Rbfox1 impairs BDNF-dependent LTP which can be rescued by genetically restoring TrkB.T1 levels. RNA-seq analysis of hippocampi with upregulation of Rbfox1 in conjunction with the specific increase of TrkB.T1 isoform expression also shows that the genes affected by Rbfox1 gain of function are surprisingly different from those influenced by Rbfox1 deletion. These findings not only identify TrkB as a major target of Rbfox1 pathophysiology but also suggest that gain or loss of function of Rbfox1 regulate different genetic landscapes.

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  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.7554/eLife.49673
  3. PMID: 31429825
  4. View record in Web of Science®
  5. WOS: 000483988600001
  6. PII : 49673

Library Notes

  1. Fiscal Year: FY2018-2019
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