期刊
MOLECULAR NEUROBIOLOGY
卷 53, 期 7, 页码 4701-4712出版社
SPRINGER
DOI: 10.1007/s12035-015-9383-z
关键词
Matrix metalloproteinase 9 (MMP-9); miR-132; Structural plasticity of dendritic spines
资金
- National Science Center [Harmonia 2013/08/M/NZ4/00650]
- Preludium from the Polish National Science Center [2012/07/N/NZ3/01509]
- Foundation for Polish Science, FNP TEAM
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.
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