TY - JOUR TI - Rbfox1 up-regulation impairs BDNF-dependent hippocampal LTP by dysregulating TrkB isoform expression levels AU - Tomassoni-Ardori, Francesco AU - Fulgenzi, Gianluca AU - Becker, Jodi AU - Barrick, Colleen AU - Palko, Mary Ellen AU - Kuhn, Skyler AU - Koparde, Vishal AU - Cam, Maggie AU - Yanpallewar, Sudhirkumar AU - Oberdoerffer, Shalini AU - Tessarollo, Lino A2 - Chao, Moses V A2 - Westbrook, Gary L VL - 8 PY - 2019 DA - 2019/08/20 SP - e49673 C1 - eLife 2019;8:e49673 DO - 10.7554/eLife.49673 UR - https://doi.org/10.7554/eLife.49673 AB - 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. KW - RNA regulation KW - neurotrophins KW - RbFox KW - TrkB JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -