RT Journal Article SR Electronic T1 The RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA Metabolism and Regulates Synaptic NMDA Receptors in Hippocampal Neurons JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0268-17.2017 DO 10.1523/ENEURO.0268-17.2017 VO 4 IS 6 A1 Graciano Leal A1 Diogo Comprido A1 Pasqualino de Luca A1 Eduardo Morais A1 Luís Rodrigues A1 Miranda Mele A1 Ana R. Santos A1 Rui O. Costa A1 Maria Joana Pinto A1 Sudarshan Patil A1 Birgitte Berentsen A1 Pedro Afonso A1 Laura Carreto A1 Ka Wan Li A1 Paulo Pinheiro A1 Ramiro D. Almeida A1 Manuel A. S. Santos A1 Clive R. Bramham A1 Carlos B. Duarte YR 2017 UL http://www.eneuro.org/content/4/6/ENEURO.0268-17.2017.abstract AB Brain-derived neurotrophic factor (BDNF) is an important mediator of long-term synaptic potentiation (LTP) in the hippocampus. The local effects of BDNF depend on the activation of translation activity, which requires the delivery of transcripts to the synapse. In this work, we found that neuronal activity regulates the dendritic localization of the RNA-binding protein heterogeneous nuclear ribonucleoprotein K (hnRNP K) in cultured rat hippocampal neurons by stimulating BDNF-Trk signaling. Microarray experiments identified a large number of transcripts that are coimmunoprecipitated with hnRNP K, and about 60% of these transcripts are dissociated from the protein upon stimulation of rat hippocampal neurons with BDNF. In vivo studies also showed a role for TrkB signaling in the dissociation of transcripts from hnRNP K upon high-frequency stimulation (HFS) of medial perforant path-granule cell synapses of male rat dentate gyrus (DG). Furthermore, treatment of rat hippocampal synaptoneurosomes with BDNF decreased the coimmunoprecipitation of hnRNP K with mRNAs coding for glutamate receptor subunits, Ca2+- and calmodulin-dependent protein kinase IIβ (CaMKIIβ) and BDNF. Downregulation of hnRNP K impaired the BDNF-induced enhancement of NMDA receptor (NMDAR)-mediated mEPSC, and similar results were obtained upon inhibition of protein synthesis with cycloheximide. The results demonstrate that BDNF regulates specific populations of hnRNP-associated mRNAs in neuronal dendrites and suggests an important role of hnRNP K in BDNF-dependent forms of synaptic plasticity.