Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking
Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking
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DOI：
10.7554/elife.14694
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发表时间：
2016-08
期刊：
影响因子：
7.7
通讯作者：
André Voelzmann;Pilar Okenve-Ramos;Yue Qu;Monika Chojnowska-Monga;Manuela del Caño-Espinel;A. Prokop;N. Sánchez-Soriano
中科院分区：
文献类型：
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作者：
André Voelzmann;Pilar Okenve-Ramos;Yue Qu;Monika Chojnowska-Monga;Manuela del Caño-Espinel;A. Prokop;N. Sánchez-Soriano
在发育和衰老过程中调节突触数量的机制对正常的大脑功能至关重要，并与包括痴呆症在内的大脑疾病密切相关。使用果蝇，我们证明了微管相关蛋白Tau在调节突触数量中的作用，从而揭示了正常Tau的重要细胞需求。在这种情况下，我们发现Tau与微管结合spectraplakins显示出很强的功能重叠，在两种不同的神经退行性因子之间建立了新的联系。Tau和spectraplakin Short Stop作用于三步调节级联的上游，确保突触蛋白的充分递送。该级联反应涉及微管稳定性作为初始触发器，JNK信号传导作为中央介质，驱动蛋白-3介导的轴突运输作为关键效应器。这种级联反应在发育（突触形成）和衰老（突触维持）过程中同样起作用。因此，我们的研究结果为Tau缺陷个体的智力残疾以及包括阿尔茨海默病在内的痴呆症的早期突触丧失提出了新的解释。DOI：http://dx.doi.org/10.7554/eLife.14694.001网站
The mechanisms regulating synapse numbers during development and ageing are essential for normal brain function and closely linked to brain disorders including dementias. Using Drosophila, we demonstrate roles of the microtubule-associated protein Tau in regulating synapse numbers, thus unravelling an important cellular requirement of normal Tau. In this context, we find that Tau displays a strong functional overlap with microtubule-binding spectraplakins, establishing new links between two different neurodegenerative factors. Tau and the spectraplakin Short Stop act upstream of a three-step regulatory cascade ensuring adequate delivery of synaptic proteins. This cascade involves microtubule stability as the initial trigger, JNK signalling as the central mediator, and kinesin-3 mediated axonal transport as the key effector. This cascade acts during development (synapse formation) and ageing (synapse maintenance) alike. Therefore, our findings suggest novel explanations for intellectual disability in Tau deficient individuals, as well as early synapse loss in dementias including Alzheimer’s disease. DOI: http://dx.doi.org/10.7554/eLife.14694.001