Amyloid precursor protein promotes post-developmental neurite arborization in the Drosophila brain
Amyloid precursor protein promotes post-developmental neurite arborization in the Drosophila brain
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DOI：
10.1038/sj.emboj.7600757
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发表时间：
2005-08-17
期刊：
影响因子：
11.4
通讯作者：
Hassan, BA
中科院分区：
文献类型：
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作者：
Leyssen, M;Ayaz, D;Hassan, BA
在发育过程中以及损伤后调节神经突生长的机制是理解正常和病理条件下大脑布线和功能的关键。淀粉样前体蛋白（APP）参与阿尔茨海默病（AD）的发病机制。然而，其在中枢神经系统中的生理作用尚不清楚。APP和细胞内信号分子之间的许多物理相互作用已被描述，但它们的功能相关性仍不清楚。我们在这里表明，人类APP和果蝇APP样（APPL）可以诱导发育后轴突树枝化，这严重依赖于保守的基序在C-末端，并需要与Abelson（Abl）酪氨酸激酶的相互作用。脑损伤诱导果蝇神经元APPL上调，与appl（d）突变果蝇创伤后死亡率增加相关。最后，我们还发现了APP和JNK应激激酶级联反应之间的相互作用。我们的研究结果表明APP在创伤性脑损伤后轴突生长中的作用。
The mechanisms regulating the outgrowth of neurites during development, as well as after injury, are key to the understanding of the wiring and functioning of the brain under normal and pathological conditions. The amyloid precursor protein ( APP) is involved in the pathogenesis of Alzheimer's disease ( AD). However, its physiological role in the central nervous system is not known. Many physical interactions between APP and intracellular signalling molecules have been described, but their functional relevance remains unclear. We show here that human APP and Drosophila APP-Like ( APPL) can induce postdevelopmental axonal arborization, which depends critically on a conserved motif in the C-terminus and requires interaction with the Abelson (Abl) tyrosine kinase. Brain injury induces APPL upregulation in Drosophila neurons, correlating with increased posttraumatic mortality in appl(d) mutant flies. Finally, we also found interactions between APP and the JNK stress kinase cascade. Our findings suggest a role for APP in axonal outgrowth after traumatic brain injury.