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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
Author: Leal, Graciano
Comprido, Diogo
Luca, Pasqualino de
Morais, Eduardo
Rodrigues, Luís
Mele, Miranda
Santos, Ana R.
Costa, Rui O.
Pinto, Maria Joana
Patil, Sudarshan
Berentsen, Birgitte
Afonso, Pedro
Carreto, Laura
Ka Wan Li
Pinheiro, Paulo
Almeida, Ramiro D.
Santos, Manuel A. S.
Bramham, Clive R.
Duarte, Carlos B.
Keywords: BDNF
Local translation
Long-term synaptic potentiation
NMDA receptors
RNA transport
Issue Date: 2017
Publisher: Society for Neuroscience: eNeuro
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.
Peer review: yes
DOI: 10.1523/ENEURO.0268-17.2017
Appears in Collections:IBIMED - Artigos
DCM - Artigos

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