Par3 regulates polarized convergence between APP and BACE1 in hippocampal neurons.

Abstract

The convergence between amyloid precursor protein (APP) and its β-secretase β-site APP cleaving enzyme 1 (BACE1) is a prerequisite for the generation of β-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.

• Authors: Miao Sun, Chengyu Huang, Hui Wang, Huaye Zhang
• Journal: Neurobiology of aging (Neurobiol Aging) Vol. 77 Pg. 87-93 (05 2019) ISSN: 1558-1497 [Electronic] United States
• PMID: 30784815 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Adaptor Proteins, Signal Transducing
• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Cell Adhesion Molecules
• Cell Cycle Proteins
• Pard3 protein, mouse
• Amyloid Precursor Protein Secretases
• Aspartic Acid Endopeptidases
• Bace1 protein, mouse

Topics

• Adaptor Proteins, Signal Transducing
• Amyloid Precursor Protein Secretases (metabolism)
• Amyloid beta-Peptides (metabolism)
• Amyloid beta-Protein Precursor (metabolism)
• Aspartic Acid Endopeptidases (metabolism)
• Axons (metabolism)
• Cell Adhesion Molecules (chemistry, metabolism, physiology)
• Cell Cycle Proteins
• Hippocampus (cytology, metabolism)
• Neurons (metabolism)
• Protein Binding
• Protein Domains
• Protein Transport (genetics)