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Cited by 10Alzheimer's disease research and treatmentsCellular transport and secretionNeuroscience and Neuropharmacology Research

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Par3 regulates polarized convergence between APP and BACE1 in hippocampal neurons

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Sun, Miao, Huang, Chengyu, Wang, Hui, Zhang, Huaye·2019·Neurobiology of Aging
DOI 10.1016/j.neurobiolaging.2019.01.023PMC PMC6528466
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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.

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Metadata

Authors
Sun, M., Huang, C., Wang, H., & Zhang, H.
Affiliations
  • Rutgers, The State University of New Jersey (US)
  • Nantong University (CN)
Corresponding author
  • Sun, Miao
  • Zhang, Huaye
ORCID
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2019-05
Volume
77
Pages
87-93
ISSN
0197-4580 (ISSN-L)
DOI
10.1016/j.neurobiolaging.2019.01.023
PMC
PMC6528466
OpenAlex
W2911319138
Cited by
10
References
1
Citations by year
2024: 3 · 2022: 3 · 2021: 3 · 2019: 1
FWCI
1.20
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurobiology of Aging (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Natural Science Foundation of China (31500845)
  • Foundation for the National Institutes of Health (NS089578)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
Par3, amyloid precursor protein, BACE1, beta-secretase, Alzheimer's disease, hippocampal neurons, PDZ domain, APP trafficking
MeSH terms
Protein Domains, Axons, Hippocampus, Neurons, Protein Binding, Cell Adhesion Molecules, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Amyloid beta-Protein Precursor, Cell Cycle Proteins, Protein Transport, Adaptor Proteins, Signal Transducing, Amyloid Precursor Protein Secretases

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