A microRNA‐129‐5p/Rbfox crosstalk coordinates homeostatic downscaling of excitatory synapses
| العنوان: | A microRNA‐129‐5p/Rbfox crosstalk coordinates homeostatic downscaling of excitatory synapses |
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| المؤلفون: | Cristina R. Reschke, Ayla Aksoy-Aksel, Norman Delanty, Morten T. Venø, Thomas Braun, Sebastian Bauer, Braxton A. Norwood, Michael A. Farrell, Donncha F. O’Brien, Roberto Fiore, Franziska Metge, Christoph Dieterich, Rana Raoof, Silvia Bicker, Felix Rosenow, David C. Henshall, Gary P. Brennan, Gerhard Schratt, Marcus Krüger, Marek Rajman, Sharof Khudayberdiev, Jørgen Kjems |
| المصدر: | Rajman, M, Metge, F, Fiore, R, Khudayberdiev, S, Aksoy-Aksel, A, Bicker, S, Reschke, C R, Raoof, R, Brennan, G P, Delanty, N, Farrell, M A, O'Brien, D F, Bauer, S, Norwood, B, Veno, M T, Krueger, M, Braun, T, Kjems, J, Rosenow, F, Henshall, D C, Dieterich, C & Schratt, G 2017, ' A microRNA-129-5p/Rbfox crosstalk coordinates homeostatic downscaling of excitatory synapses ', E M B O Journal, vol. 36, no. 12, pp. 1770-1787 . https://doi.org/10.15252/embj.201695748Test |
| بيانات النشر: | EMBO, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Doublecortin Domain Proteins, 0301 basic medicine, Proteome, MICRORNAS, RNA-binding protein, Bioinformatics, Hippocampus, Epileptogenesis, Mice, SYNAPTIC PLASTICITY, Homeostatic plasticity, Picrotoxin, Synaptic scaling, microRNA, biology, General Neuroscience, Articles, Crosstalk (biology), Excitatory postsynaptic potential, RNA Splicing Factors, Microtubule-Associated Proteins, EXPRESSION, Doublecortin Protein, PROTEINS, AMPA receptor, General Biochemistry, Genetics and Molecular Biology, homeostatic plasticity, Plasma Membrane Calcium-Transporting ATPases, 03 medical and health sciences, Animals, synaptic scaling, VISUAL-CORTEX, Molecular Biology, General Immunology and Microbiology, AMPA RECEPTORS, Gene Expression Profiling, Neuropeptides, STATUS EPILEPTICUS, Computational Biology, MAMMALIAN BRAIN, Doublecortin, MicroRNAs, 030104 developmental biology, Gene Expression Regulation, MESSENGER-RNA LOCALIZATION, Synapses, Synaptic plasticity, biology.protein, epilepsy, DENDRITIC SPINE DEVELOPMENT, Neuroscience |
| الوصف: | Synaptic downscaling is a homeostatic mechanism that allows neurons to reduce firing rates during chronically elevated network activity. Although synaptic downscaling is important in neural circuit development and epilepsy, the underlying mechanisms are poorly described. We performed small RNA profiling in picrotoxin (PTX)‐treated hippocampal neurons, a model of synaptic downscaling. Thereby, we identified eight microRNAs (miRNAs) that were increased in response to PTX, including miR‐129‐5p, whose inhibition blocked synaptic downscaling in vitro and reduced epileptic seizure severity in vivo . Using transcriptome, proteome, and bioinformatic analysis, we identified the calcium pump Atp2b4 and doublecortin (Dcx) as miR‐129‐5p targets. Restoring Atp2b4 and Dcx expression was sufficient to prevent synaptic downscaling in PTX‐treated neurons. Furthermore, we characterized a functional crosstalk between miR‐129‐5p and the RNA‐binding protein (RBP) Rbfox1. In the absence of PTX, Rbfox1 promoted the expression of Atp2b4 and Dcx. Upon PTX treatment, Rbfox1 expression was downregulated by miR‐129‐5p, thereby allowing the repression of Atp2b4 and Dcx. We therefore identified a novel activity‐dependent miRNA/RBP crosstalk during synaptic scaling, with potential implications for neural network homeostasis and epileptogenesis. |
| تدمد: | 1460-2075 0261-4189 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::46fb481b7f9a93f21613c2cc0cffbd33Test https://doi.org/10.15252/embj.201695748Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....46fb481b7f9a93f21613c2cc0cffbd33 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602075 02614189 |
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