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Title: The RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA Metabolism and Regulates Synaptic NMDA Receptors in Hippocampal Neurons
Authors: Leal, Graciano 
Comprido, Diogo 
Luca, Pasqualino De 
Morais, Eduardo Manuel Firmo 
Rodrigues, Luís
Mele, Miranda 
Santos, Ana R. 
Costa, Rui O. 
Pinto, Maria Joana 
Patil, Sudarshan
Berentsen, Birgitte
Afonso, Pedro M. 
Carreto, Laura
Li, Ka Wan
Pinheiro, Paulo S. 
Almeida, Ramiro D. 
Santos, Manuel A. S. 
Bramham, Clive R.
Duarte, Carlos B. 
Keywords: BDNF; local translation; long-term synaptic potentiation; neurotrophins; NMDA receptors; RNA transport
Issue Date: 2017
Publisher: Society for Neuroscience
Project: This work was supported by grants from the European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme (project CENTRO-01-0145-FEDER-000008:BrainHealth 2020), COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT - Fundação para a Ciência e a Tecnologia, I.P. (projects POCI-01-0145-FEDER-007440, PTDC/SAU-NEU/ 104297/2008 (to C.B.D.), PTDC/BEX-BCM/2121/2014 (to M.A.S.S.), UID/NEU/ 04539/2013, UID/BIM/4501/2013, SFRH/BPD/115546/2016 (to M.M.) and SFRH/BPD/84593/2012 (to R.O.C.)), GenomePT, Liga Portuguesa Contra a Epilepsia, The Research Council of Norway (Grants 204861 and 199355, to C.R.B.), and the Norwegian Financial Mechanism (Grant EMP128, to C.R.B.). 
Serial title, monograph or event: eNeuro
Volume: 4
Issue: 6
Abstract: 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.
ISSN: 2373-2822
DOI: 10.1523/ENEURO.0268-17.2017
Rights: openAccess
Appears in Collections:IIIUC - Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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