极性蛋白Par3通过内吞衔接蛋白Numb调节淀粉样前体蛋白（APP）的运输和加工。
The polarity protein Par3 regulates APP trafficking and processing through the endocytic adaptor protein Numb.
作者信息
Sun Miao, Asghar Suwaiba Z, Zhang Huaye
机构信息
Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, United States.
Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, United States.
出版信息
Neurobiol Dis. 2016 Sep;93:1-11. doi: 10.1016/j.nbd.2016.03.022. Epub 2016 Apr 9.
The processing of amyloid precursor protein (APP) into β-amyloid peptide (Aβ) is a key step in the pathogenesis of Alzheimer's disease (AD), and trafficking dysregulations of APP and its secretases contribute significantly to altered APP processing. Here we show that the cell polarity protein Par3 plays an important role in APP processing and trafficking. We found that the expression of full length Par3 is significantly decreased in AD patients. Overexpression of Par3 promotes non-amyloidogenic APP processing, while depletion of Par3 induces intracellular accumulation of Aβ. We further show that Par3 functions by regulating APP trafficking. Loss of Par3 decreases surface expression of APP by targeting APP to the late endosome/lysosome pathway. Finally, we show that the effects of Par3 are mediated through the endocytic adaptor protein Numb, and Par3 functions by interfering with the interaction between Numb and APP. Together, our studies show a novel role for Par3 in regulating APP processing and trafficking.
淀粉样前体蛋白（APP）加工成β-淀粉样肽（Aβ）是阿尔茨海默病（AD）发病机制中的关键步骤，APP及其分泌酶的运输失调对APP加工改变有显著影响。在此我们表明，细胞极性蛋白Par3在APP加工和运输中起重要作用。我们发现AD患者中全长Par3的表达显著降低。Par3的过表达促进非淀粉样生成性APP加工，而Par3的缺失诱导Aβ在细胞内积累。我们进一步表明Par3通过调节APP运输发挥作用。Par3的缺失通过将APP靶向晚期内体/溶酶体途径降低APP的表面表达。最后，我们表明Par3的作用是通过内吞衔接蛋白Numb介导的，并且Par3通过干扰Numb与APP之间的相互作用发挥作用。总之，我们的研究表明Par3在调节APP加工和运输中具有新作用。
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