Studies on the activity-dependent translational control in neurons

突触周围区域的活动依赖性局部翻译与突触范围内的功能和形态改变有关。然而，局部翻译激活的分子机制尚未阐明。我们已经表明，在神经元树突的局部蛋白质合成和翻译激活上调脑源性神经营养因子（BDNF）在雷帕霉素敏感的方式。与此同时，BDNF激活树突中的哺乳动物雷帕霉素靶蛋白（mTOR）信号通路。BDNF还通过mTOR途径增强延伸过程。通过雷帕霉素抑制mTOR活性和通过siRNA敲低mTOR完全抑制BDNF的作用。目前的结果表明，mTOR依赖的翻译激活在多个过程中是必要的上调局部蛋白质合成的神经元树突。我们进一步证明了mTOR依赖的翻译激活发生在可塑性事件中，如CNS中的LTP和空间记忆范式。由于雷帕霉素消除了这些效应，mTOR依赖性翻译激活对于某些类型的神经可塑性至关重要。

Activity-dependent local translation at the perisynaptic area is implicated in synapse-wide alterations of function and morphology. The molecular mechanisms of local translation activation, however, have yet to be illuminated. We have shown that local protein synthesis and translational activation in neuronal dendrites were up-regulated by brain-derived neurotrophic factor (BDNF) in a rapamycin-sensitive manner. In parallel, BDNF activates of mammalian target of rapamycin (mTOR) signaling pathways in dendrites. BDNF also enhances elongation process through the mTOR pathway. Inhibition of mTOR activity by rapamycin and knockdown of mTOR by siRNA completely suppresses the action of BDNF.The present results indicate that mTOR-dependent translation activation at multiple processes is essential for the up-regulation of local protein synthesis in neuronal dendrites. We further showed the evidences that mTOR-dependent translational activation occurred during plastic event, such as LTP and spatial memory paradigms in the CNS. As rapamycin canceled these effects, mTOR-dependent translational activation is essential for the certain types of neural plasticity.