NEUROBIOLOGY OF AGING | 卷:77 |
Par3 regulates polarized convergence between APP and BACE1 in hippocampal neurons | |
Article | |
Sun, Miao1  Huang, Chengyu2  Wang, Hui1,2  Zhang, Huaye1  | |
[1] Rutgers Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA | |
[2] Nantong Univ, Sch Pharm, Dept Pharmacol, Nantong, Jiangsu, Peoples R China | |
关键词: Par3; APP; BACE1; Trafficking; Alzheimer's disease; | |
DOI : 10.1016/j.neurobiolaging.2019.01.023 | |
来源: Elsevier | |
【 摘 要 】
The convergence between amyloid precursor protein (APP) and its beta-secretase beta-site APP cleaving enzyme 1 (BACE1) is a prerequisite for the generation of beta-amyloid peptide, a key pathogenic agent for Alzheimer's disease. Yet the underlying molecular mechanisms regulating their convergence remain unclear. Here, we show that the polarity protein partitioning-defective 3 (Par3) regulates the polarized convergence between APP and BACE1 in hippocampal neurons. Par3 forms a complex with BACE1 through its first PDZ domain, which is important for regulating BACE1 endosome-to-TGN trafficking. In the absence of Par3, there is an increase in the convergence between internalized APP and BACE1. In hippocampal neurons, loss of Par3 leads to increased APP and BACE1 convergence in axons but not in dendrites. This polarized convergence mainly occurs in retrograde or stalled axonal late endocytic organelles and is likely due to compartment-specific regulation of APP trafficking by Par3. Together, our data show a novel function for Par3 in regulating polarized convergence between APP and BACE1 in hippocampal neurons. (C) 2019 Elsevier Inc. All rights reserved.
【 授权许可】
Free
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