Sigrist S J, Thiel P R, Reiff D F, Lachance P E, Lasko P, Schuster C M
Friedrich-Miescher-Laboratorium der Max-Planck-Gesellschaft, Tübingen, Germany.
Nature. 2000 Jun 29;405(6790):1062-5. doi: 10.1038/35016598.
Long-term synaptic plasticity may be associated with structural rearrangements within the neuronal circuitry. Although the molecular mechanisms governing such activity-controlled morphological alterations are mostly elusive, polysomal accumulations at the base of developing dendritic spines and the activity-induced synthesis of synaptic components suggest that localized translation is involved during synaptic plasticity. Here we show that large aggregates of translational components as well as messenger RNA of the postsynaptic glutamate receptor subunit DGluR-IIA are localized within subsynaptic compartments of larval neuromuscular junctions of Drosophila melanogaster. Genetic models of junctional plasticity and genetic manipulations using the translation initiation factors eIF4E and poly(A)-binding protein showed an increased occurrence of subsynaptic translation aggregates. This was associated with a significant increase in the postsynaptic DGluR-IIA protein levels and a reduction in the junctional expression of the cell-adhesion molecule Fasciclin II. In addition, the efficacy of junctional neurotransmission and the size of larval neuromuscular junctions were significantly increased. Our results therefore provide evidence for a postsynaptic translational control of long-term junctional plasticity.
长期突触可塑性可能与神经回路内的结构重排有关。尽管控制这种活动控制的形态改变的分子机制大多难以捉摸，但发育中的树突棘基部的多核糖体积累以及突触成分的活动诱导合成表明，局部翻译参与了突触可塑性过程。在这里，我们表明翻译成分的大聚集体以及突触后谷氨酸受体亚基DGluR-IIA的信使核糖核酸定位于黑腹果蝇幼虫神经肌肉接头的突触下区室。接头可塑性的遗传模型以及使用翻译起始因子eIF4E和聚腺苷酸结合蛋白的基因操作显示，突触下翻译聚集体的出现增加。这与突触后DGluR-IIA蛋白水平的显著增加以及细胞粘附分子Fasciclin II的接头表达减少有关。此外，接头神经传递的效率和幼虫神经肌肉接头的大小显著增加。因此，我们的结果为长期接头可塑性的突触后翻译控制提供了证据。
