An activity-regulated microRNA, miR-188, controls dendritic plasticity and synaptic transmission by downregulating neuropilin-2.
An activity-regulated microRNA, miR-188, controls dendritic plasticity and synaptic transmission by downregulating neuropilin-2.
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DOI：
10.1523/jneurosci.6471-11.2012
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发表时间：
2012-04-18
期刊：
影响因子：
--
通讯作者：
Kim HS
中科院分区：
文献类型：
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作者：
Lee K;Kim JH;Kwon OB;An K;Ryu J;Cho K;Suh YH;Kim HS
microRNA（miRNAs）最近被认为是调节各种生物系统（包括成熟的中枢神经系统）中的许多细胞特征的关键参与者，其通过对mRNA的稳定性和翻译施加调节控制。尽管有相当多的证据表明miRNA的调控功能，但参与突触传递和可塑性调控的miRNA种类的身份以及这些miRNA发挥功能作用的机制在很大程度上仍然未知。在本研究中，发现microRNA-188（miR-188）的表达通过诱导长时程增强（LTP）而上调。神经纤毛蛋白-2（Nrp-2）是miR-188可能的分子靶点之一，其蛋白水平在LTP诱导过程中降低。我们还证实，Nrp-2的3 '-UTR的荧光素酶活性通过用miR-188寡核苷酸处理而不是用乱序miRNA寡核苷酸处理而降低。Nrp-2是脑信号蛋白3F的受体，脑信号蛋白3F是脊髓发育和突触结构的负调节因子。此外，miR-188特异性地挽救了大鼠原代培养的海马神经元中由Nrp-2表达诱导的树突棘密度的降低。此外，miR-188抵消了由Nrp-2表达诱导的大鼠原代培养海马神经元中微型EPSC频率的降低。这些发现表明，miR-188通过调节Nrp-2表达来微调突触可塑性。
MicroRNAs (miRNAs) have recently come to be viewed as critical players that modulate a number of cellular features in various biological systems including the mature central nervous system by exerting regulatory control over the stability and translation of mRNAs. Despite considerable evidence for the regulatory functions of miRNAs, the identities of the miRNA species that are involved in the regulation of synaptic transmission and plasticity and the mechanisms by which these miRNAs exert functional roles remain largely unknown. In the present study, the expression of microRNA-188 (miR-188) was found to be upregulated by the induction of long-term potentiation (LTP). The protein level of neuropilin-2 (Nrp-2), one of the possible molecular targets for miR-188, was decreased during LTP induction. We also confirmed that the luciferase activity of the 3’-UTR of Nrp-2 was diminished by treatment with a miR-188 oligonucleotide but not with a scrambled miRNA oligonucleotide. Nrp-2 serves as a receptor for semaphorin 3F, which is a negative regulator of spine development and synaptic structure. In addition, miR-188 specifically rescued the reduction in dendritic spine density induced by Nrp-2 expression in hippocampal neurons from rat primary culture. Furthermore, miR-188 counteracted the decrease in the miniature EPSC frequency induced by Nrp-2 expression in hippocampal neurons from rat primary culture. These findings suggest that miR-188 serves to fine-tune synaptic plasticity by regulating Nrp-2 expression.