miR-146a-5p 对 mGluR 依赖性 MAP1B 翻译和 AMPA 受体内吞作用的调节。
Modulation of mGluR-dependent MAP1B translation and AMPA receptor endocytosis by microRNA miR-146a-5p.
机构信息
Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan, Republic of China.
出版信息
J Neurosci. 2013 May 22;33(21):9013-20. doi: 10.1523/JNEUROSCI.5210-12.2013.
Abstract
The translation of dendritic microtubule-associated protein 1B (MAP1B) is exaggerated upon group I mGluR activation leading to AMPA receptor (AMPAR) endocytosis and consequent long-term depression. However, the mechanisms of regulation of MAP1B protein synthesis in the mature dendrites remain unclear. Here we have identified miR-146a-5p that targets the 3' UTR of MAP1B mRNA and represses its translation. Inhibition of the endogenous miR-146a-5p in mouse cultured hippocampal neurons triggers an increase of the dendritic MAP1B protein as well as the internalization of AMPARs, resulting in a decline in synaptic transmission. Conversely, enforced expression of miR-146a-5p inhibits MAP1B translation and attenuates group I mGluR-induced AMPAR endocytosis. Moreover, siRNA-mediated knockdown of MAP1B recovers the impairment of synaptic transmission caused by inhibition of miR-146a-5p. These results reveal that miR-146a-5p modulates the synaptic plasticity via repression of MAP1B protein synthesis.
摘要
树突微管相关蛋白 1B (MAP1B) 的翻译在 I 型 mGluR 激活后被夸大，导致 AMPA 受体 (AMPAR) 内吞作用和随后的长时程抑郁。然而，成熟树突中 MAP1B 蛋白合成的调节机制仍不清楚。在这里，我们鉴定出了靶向 MAP1B mRNA 3' UTR 的 miR-146a-5p，并抑制其翻译。在培养的海马神经元中抑制内源性 miR-146a-5p 会触发树突状 MAP1B 蛋白增加以及 AMPAR 内吞作用，从而导致突触传递减少。相反，强制表达 miR-146a-5p 抑制 MAP1B 翻译并减弱 I 型 mGluR 诱导的 AMPAR 内吞作用。此外，MAP1B 的 siRNA 介导的敲低可恢复抑制 miR-146a-5p 引起的突触传递损伤。这些结果表明，miR-146a-5p 通过抑制 MAP1B 蛋白合成来调节突触可塑性。
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