The RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA Metabolism and Regulates Synaptic NMDA Receptors in Hippocampal Neurons
| Autor: | Birgitte Berentsen, Miranda Mele, Ramiro D. Almeida, Rui Costa, Luís Rodrigues, Ana Rita Santos, Clive R. Bramham, Laura Carreto, Carlos B. Duarte, Maria J. Pinto, Pedro M. Afonso, Pasqualino De Luca, Manuel A. S. Santos, Eduardo Morais, Paulo S. Pinheiro, Diogo Comprido, Sudarshan Patil, Graciano Leal, Ka Wan Li |
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| Přispěvatelé: | Molecular and Cellular Neurobiology, AIMMS, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Neurodegeneration |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
long-term synaptic potentiation Neuronal Excitability Tropomyosin receptor kinase B Hippocampal formation neurotrophins Hippocampus RNA Transport Heterogeneous-Nuclear Ribonucleoprotein K Rats Sprague-Dawley 0302 clinical medicine local translation Cells Cultured 0303 health sciences Chemistry General Neuroscience Glutamate receptor Long-term potentiation General Medicine New Research Cell biology NMDA receptor Female Receptors N-Methyl-D-Aspartate NMDA receptors 03 medical and health sciences Long-term synaptic potentiation Animals Outbred Strains Journal Article Animals Humans RNA Messenger Rats Wistar 030304 developmental biology Brain-Derived Neurotrophic Factor Excitatory Postsynaptic Potentials Dendrites Microarray Analysis HEK293 Cells BDNF nervous system 6.1 Synaptic plasticity Synapses RNA transport Microelectrodes 030217 neurology & neurosurgery Synaptosomes |
| Zdroj: | Leal, G, Comprido, D, de Luca, P, Morais, E, Rodrigues, L, Mele, M, Santos, A R, Costa, R O, Pinto, M J, Patil, S, Berentsen, B, Afonso, P, Carreto, L, Li, K W, Pinheiro, P, Almeida, R D, Santos, M A S, Bramham, C R & Duarte, C B 2017, ' The RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA Metabolism and Regulates Synaptic NMDA Receptors in Hippocampal Neurons ', eNeuro, vol. 4, no. 6, e0268-17.2017 . https://doi.org/10.1523/ENEURO.0268-17.2017 eNeuro Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP eNeuro, 4(6):e0268-17.2017. Society for Neuroscience |
| ISSN: | 2373-2822 |
| Popis: | 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 vivostudies 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. |
| Databáze: | OpenAIRE |
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