miR-132 Regulates Dendritic Spine Structure by Direct Targeting of Matrix Metalloproteinase 9 mRNA.
miR-132 Regulates Dendritic Spine Structure by Direct Targeting of Matrix Metalloproteinase 9 mRNA.
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DOI：
10.1007/s12035-015-9383-z
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发表时间：
2016-09
影响因子：
5.1
通讯作者：
Dziembowska M
中科院分区：
文献类型：
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作者：
Jasińska M;Miłek J;Cymerman IA;Łęski S;Kaczmarek L;Dziembowska M
Mir-132是一种神经元活性调节的microRNA，控制树突棘的形态和神经元传递。类似的活动最近已归因于基质金属蛋白酶-9（MMP-9），一种突触外蛋白酶。在本研究中，我们提供的证据表明，miR-132直接调节神经元中的MMP-9 mRNA，以调节突触可塑性。利用荧光素酶报告系统，我们发现miR-132与MMP-9 mRNA的3 'UTR结合，调节其在神经元中的表达。miR-132在神经元中的过表达降低了内源性MMP-9蛋白的分泌水平。在突触神经体中，代谢型谷氨酸受体（mGluR）诱导的信号刺激miR-132从多聚核糖体部分解离，并将其转移到含有信使核糖核蛋白（mRNP）的部分。此外，我们证明了miR-132在具有增加的突触MMP-9水平的Fmr 1 KO小鼠的培养的海马神经元中的过表达引起树突棘头的增大，这是先前与增强的突触可塑性有关的过程。我们认为活性依赖性miR-132通过基质金属蛋白酶9调节树突棘的结构可塑性。
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.