Brain-derived neurotrophic factor induces mammalian target of rapamycin-dependent local activation of translation machinery and protein synthesis in neuronal dendrites
Brain-derived neurotrophic factor induces mammalian target of rapamycin-dependent local activation of translation machinery and protein synthesis in neuronal dendrites
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DOI：
10.1523/jneurosci.1427-04.2004
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发表时间：
2004-11-03
影响因子：
5.3
通讯作者：
Nawa, H
中科院分区：
文献类型：
--
作者：
Takei, N;Inamura, N;Nawa, H
在神经元中，突触周或树突翻译涉及由神经活动触发的突触范围的功能和形态改变。然而，控制局部翻译激活的分子机制尚未阐明。在这里，我们表明，局部蛋白质合成和翻译激活神经元树突上调脑源性神经营养因子（BDNF）的雷帕霉素和小干扰RNA的哺乳动物雷帕霉素靶（mTOR）敏感的方式。与此同时，BDNF诱导树突和突触神经体部分中tuberin的磷酸化和mTOR的活化。mTOR激活刺激涉及eIF 4 E/4 E结合蛋白（4 EBP）和p70 S6激酶/核糖体S6蛋白的翻译起始过程。BDNF诱导的4 EBP在孤立的树突磷酸化。此外，局部应用BDNF树突触发S6磷酸化在一个有限的区域。总之，这些数据表明，mTOR依赖的翻译激活是必不可少的上调神经元树突中的局部蛋白质合成。
In neurons, perisynaptic or dendritic translation is implicated in synapse-wide alterations of function and morphology triggered by neural activity. The molecular mechanisms controlling local translation activation, however, have yet to be elucidated. Here, we show that local protein synthesis and translational activation in neuronal dendrites are upregulated by brain-derived neurotrophic factor (BDNF) in a rapamycin and small interfering RNA specific for mammalian target of rapamycin (mTOR)-sensitive manner. In parallel, BDNF induced the phosphorylation of tuberin and the activation of mTOR in dendrites and the synaptoneurosome fraction. mTOR activation stimulated translation initiation processes involving both eIF4E/4E-binding protein (4EBP) and p70S6 kinase/ribosomal S6 protein. BDNF induced phosphorylation of 4EBP in isolated dendrites. Moreover, local puff application of BDNF to dendrites triggered S6 phosphorylation in a restricted area. Taken together, these data indicate that mTOR-dependent translation activation is essential for the upregulation of local protein synthesis in neuronal dendrites.