The polarity protein Par3 regulates APP trafficking and processing through the endocytic adaptor protein Numb

NEUROBIOLOGY OF DISEASE

卷:93

Article

Sun, Miao¹  Asghar, Suwaiba Z.¹  Zhang, Huaye¹ 

[1] Rutgers Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA

关键词: Cell polarity;    Trafficking;    Alzheimer disease;    Amyloid precursor protein (APP);    Amyloid-beta (A beta);    Par3;    Numb;   

DOI  :  10.1016/j.nbd.2016.03.022

来源: Elsevier

【 摘 要 】

The processing of amyloid precursor protein (APP) into beta-amyloid peptide (A beta) 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. Over expression of Par3 promotes non-amyloidogenic APP processing, while depletion of Par3 induces intracellular accumulation of A beta. 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. (C) 2016 Elsevier Inc. All rights reserved.

【 授权许可】

Free