Disruption of axonal transport and neuronal viability by amyloid precursor protein mutations in Drosophila
Disruption of axonal transport and neuronal viability by amyloid precursor protein mutations in Drosophila
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DOI：
10.1016/s0896-6273(01)00496-2
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发表时间：
2001-11-08
期刊：
影响因子：
16.2
通讯作者：
Goldstein, LSB
中科院分区：
文献类型：
--
作者：
Gunawardena, S;Goldstein, LSB
我们验证了淀粉样前体蛋白（APP）及其相关蛋白作为驱动蛋白I的囊泡受体蛋白的假设。果蝇APP样基因（Appl）的缺失或人APP 695或APPL构建体的过表达引起了类似于驱动蛋白和动力蛋白突变体的轴突运输表型。驱动蛋白-I表达的遗传减少增强，而动力蛋白表达的遗传减少抑制了这些表型。缺失APP 695或APPL的C末端，包括驱动蛋白结合区，破坏APP 695和APPL的轴突运输，并废除细胞器积累表型。神经元凋亡仅由含有APP 695的C-末端和A β区域的构建体的过表达诱导。我们讨论了轴突运输中断可能在阿尔茨海默病的神经退行性病理学中发挥作用的可能性。
We tested the hypothesis that amyloid precursor protein (APP) and its relatives function as vesicular receptor proteins for kinesin-I. Deletion of the Drosophila APP-like gene (Appl) or overexpression of human APP695 or APPL constructs caused axonal transport phenotypes similar to kinesin and dynein mutants. Genetic reduction of kinesin-I expression enhanced while genetic reduction of dynein expression suppressed these phenotypes. Deletion of the C terminus of APP695 or APPL, including the kinesin binding region, disrupted axonal transport of APP695 and APPL and abolished the organelle accumulation phenotype. Neuronal apoptosis was induced only by overexpression of constructs containing both the C-terminal and A beta regions of APP695. We discuss the possibility that axonal transport disruption may play a role in the neurodegenerative pathology of Alzheimer's disease.