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dc.contributor.authorLeal, Graciano
dc.contributor.authorComprido, Diogo
dc.contributor.authorde Luca, Pasqualino
dc.contributor.authorMorais, Eduardo
dc.contributor.authorRodrigues, Luís
dc.contributor.authorMele, Miranda
dc.contributor.authorSantos, Ana R.
dc.contributor.authorCosta, Rui O.
dc.contributor.authorPinto, Maria Joana
dc.contributor.authorPatil, Sudarshan
dc.contributor.authorBerentsen, Birgitte
dc.contributor.authorAfonso, Pedro
dc.contributor.authorCarreto, Laura
dc.contributor.authorLi, Ka Wan
dc.contributor.authorPinheiro, Paulo
dc.contributor.authorAlmeida, Ramiro D.
dc.contributor.authorSantos, Manuel A. S.
dc.contributor.authorBramham, Clive R.
dc.contributor.authorDuarte, Carlos B.
dc.identifier.citationLeal, Comprido, de Luca, Morais, Rodrigues L, Mele, Santos A, Costa R, Pinto, Patil S, Berentsen B, Afonso P, Carreto, Li, Pinheiro, Almeida, Santos, Bramham CRE, Duarte. The RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA Metabolism and Regulates Synaptic NMDA Receptors in Hippocampal Neurons. eNeuro. 2017;4(6):e0268-17.2017eng
dc.description.abstractBrain-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.eng
dc.publisherSociety for Neuroscienceeng
dc.rightsAttribution CC BYeng
dc.subjectlocal translationeng
dc.subjectlong-term synaptic potentiationeng
dc.subjectNMDA receptorseng
dc.subjectRNA transporteng
dc.titleThe RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA Metabolism and Regulates Synaptic NMDA Receptors in Hippocampal Neuronseng
dc.typeJournal articleeng
dc.rights.holderCopyright 2017 The Author(s)eng
bora.peerreviewedPeer reviewedeng
dc.type.documentJournal article
dc.relation.projectIDNorges forskningsråd: 204861
dc.relation.projectIDNorges forskningsråd: 199355

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