miR-132 Regulates Dendritic Spine Structure by Direct Targeting of Matrix Metalloproteinase 9 mRNA
| Autor: | Leszek Kaczmarek, Iwona A. Cymerman, Szymon Łęski, Magdalena Jasińska, Magdalena Dziembowska, Jacek Milek |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Dendritic spine Dendritic Spines Neuroscience (miscellaneous) Hippocampus Biology Neuronal Transmission Article miR-132 03 medical and health sciences Cellular and Molecular Neuroscience Mice microRNA Animals Humans RNA Messenger Cells Cultured Cerebral Cortex Mice Knockout Structural plasticity of dendritic spines Messenger RNA Neuronal Plasticity Cell biology Rats MicroRNAs 030104 developmental biology HEK293 Cells Neurology Matrix Metalloproteinase 9 Metabotropic glutamate receptor Synaptic plasticity Neuroscience Matrix metalloproteinase 9 (MMP-9) Synaptosomes |
| Zdroj: | Molecular Neurobiology |
| ISSN: | 1559-1182 |
| Popis: | Mir-132 is a neuronal activity-regulated microRNA that controls the morphology of dendritic spines and neuronal transmission. Similar activities have recently been attributed to matrix metalloproteinase-9 (MMP-9), an extrasynaptic protease. In the present study, we provide evidence that miR-132 directly regulates MMP-9 mRNA in neurons to modulate synaptic plasticity. With the use of luciferase reporter system, we show that miR-132 binds to the 3'UTR of MMP-9 mRNA to regulate its expression in neurons. The overexpression of miR-132 in neurons reduces the level of endogenous MMP-9 protein secretion. In synaptoneurosomes, metabotropic glutamate receptor (mGluR)-induced signaling stimulates the dissociation of miR-132 from polyribosomal fractions and shifts it towards the messenger ribonucleoprotein (mRNP)-containing fraction. Furthermore, we demonstrate that the overexpression of miR-132 in the cultured hippocampal neurons from Fmr1 KO mice that have increased synaptic MMP-9 level provokes enlargement of the dendritic spine heads, a process previously implicated in enhanced synaptic plasticity. We propose that activity-dependent miR-132 regulates structural plasticity of dendritic spines through matrix metalloproteinase 9. |
| Databáze: | OpenAIRE |
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