TY - JOUR 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 DO - 10.1523/ENEURO.0268-17.2017 VL - 4 IS - 6 SP - ENEURO.0268-17.2017 AU - Graciano Leal AU - Diogo Comprido AU - Pasqualino de Luca AU - Eduardo Morais AU - Luís Rodrigues AU - Miranda Mele AU - Ana R. Santos AU - Rui O. Costa AU - Maria Joana Pinto AU - Sudarshan Patil AU - Birgitte Berentsen AU - Pedro Afonso AU - Laura Carreto AU - Ka Wan Li AU - Paulo Pinheiro AU - Ramiro D. Almeida AU - Manuel A. S. Santos AU - Clive R. Bramham AU - Carlos B. Duarte Y1 - 2017/11/01 UR - http://www.eneuro.org/content/4/6/ENEURO.0268-17.2017.abstract N2 - 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. ER -