PMID- 29255796 OWN - NLM STAT- MEDLINE DCOM- 20180807 LR - 20220321 IS - 2373-2822 (Electronic) IS - 2373-2822 (Linking) VI - 4 IP - 6 DP - 2017 Nov-Dec TI - The RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA Metabolism and Regulates Synaptic NMDA Receptors in Hippocampal Neurons. LID - 10.1523/ENEURO.0268-17.2017 [doi] LID - ENEURO.0268-17.2017 AB - 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, Ca(2+)- and calmodulin-dependent protein kinase IIbeta (CaMKIIbeta) 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. FAU - Leal, Graciano AU - Leal G AD - CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal. FAU - Comprido, Diogo AU - Comprido D AD - CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal. FAU - de Luca, Pasqualino AU - de Luca P AUID- ORCID: 0000-0002-1113-2135 AD - CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal. FAU - Morais, Eduardo AU - Morais E AUID- ORCID: 0000-0002-1103-2070 AD - CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal. FAU - Rodrigues, Luis AU - Rodrigues L AD - CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal. FAU - Mele, Miranda AU - Mele M AUID- ORCID: 0000-0002-8627-4883 AD - CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal. FAU - Santos, Ana R AU - Santos AR AUID- ORCID: 0000-0002-0437-1146 AD - CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal. FAU - Costa, Rui O AU - Costa RO AUID- ORCID: 0000-0002-2652-7500 AD - CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal. AD - Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal. FAU - Pinto, Maria Joana AU - Pinto MJ AUID- ORCID: 0000-0001-9730-5772 AD - CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal. FAU - Patil, Sudarshan AU - Patil S AUID- ORCID: 0000-0002-6294-7959 AD - Department of Biomedicine and KG Jebsen Centre for Neuropsychiatric Disorders, University of Bergen, 5020 Bergen, Norway. FAU - Berentsen, Birgitte AU - Berentsen B AD - Department of Biomedicine and KG Jebsen Centre for Neuropsychiatric Disorders, University of Bergen, 5020 Bergen, Norway. FAU - Afonso, Pedro AU - Afonso P AD - CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal. FAU - Carreto, Laura AU - Carreto L AD - Department of Medical Sciences and Institute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal. FAU - Li, Ka Wan AU - Li KW AUID- ORCID: 0000-0001-6983-5055 AD - Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit, 1081 Amsterdam, The Netherlands. FAU - Pinheiro, Paulo AU - Pinheiro P AUID- ORCID: 0000-0002-9024-1021 AD - CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal. AD - Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal. FAU - Almeida, Ramiro D AU - Almeida RD AUID- ORCID: 0000-0001-5830-2595 AD - CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal. AD - Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal. AD - Department of Medical Sciences and Institute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal. FAU - Santos, Manuel A S AU - Santos MAS AUID- ORCID: 0000-0002-0437-1146 AD - Department of Medical Sciences and Institute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal. FAU - Bramham, Clive R AU - Bramham CR AUID- ORCID: 0000-0001-5958-7115 AD - Department of Biomedicine and KG Jebsen Centre for Neuropsychiatric Disorders, University of Bergen, 5020 Bergen, Norway. FAU - Duarte, Carlos B AU - Duarte CB AUID- ORCID: 0000-0003-1603-6721 AD - CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal. AD - Department of Life Sciences, University of Coimbra, 3000-456 Coimbra, Portugal. LA - eng PT - Journal Article DEP - 20171212 PL - United States TA - eNeuro JT - eNeuro JID - 101647362 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Heterogeneous-Nuclear Ribonucleoprotein K) RN - 0 (RNA, Messenger) RN - 0 (Receptors, N-Methyl-D-Aspartate) SB - IM MH - Animals MH - Animals, Outbred Strains MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cells, Cultured MH - Dendrites/*metabolism MH - Excitatory Postsynaptic Potentials/physiology MH - Female MH - HEK293 Cells MH - Heterogeneous-Nuclear Ribonucleoprotein K/genetics/*metabolism MH - Hippocampus/cytology/*metabolism MH - Humans MH - Male MH - Microarray Analysis MH - Microelectrodes MH - RNA Transport/physiology MH - RNA, Messenger/metabolism MH - Rats, Sprague-Dawley MH - Rats, Wistar MH - Receptors, N-Methyl-D-Aspartate/*metabolism MH - Synapses/*metabolism MH - Synaptosomes/metabolism PMC - PMC5732018 OTO - NOTNLM OT - BDNF OT - NMDA receptors OT - RNA transport OT - local translation OT - long-term synaptic potentiation OT - neurotrophins EDAT- 2017/12/20 06:00 MHDA- 2018/08/08 06:00 PMCR- 2017/12/12 CRDT- 2017/12/20 06:00 PHST- 2017/08/01 00:00 [received] PHST- 2017/10/25 00:00 [revised] PHST- 2017/11/09 00:00 [accepted] PHST- 2017/12/20 06:00 [entrez] PHST- 2017/12/20 06:00 [pubmed] PHST- 2018/08/08 06:00 [medline] PHST- 2017/12/12 00:00 [pmc-release] AID - eN-NWR-0268-17 [pii] AID - 10.1523/ENEURO.0268-17.2017 [doi] PST - epublish SO - eNeuro. 2017 Dec 12;4(6):ENEURO.0268-17.2017. doi: 10.1523/ENEURO.0268-17.2017. eCollection 2017 Nov-Dec.