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Cited by 26Alzheimer's disease research and treatmentsCellular transport and secretionDementia and Cognitive Impairment Research

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

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Sun, Miao, Asghar, Suwaiba Z., Zhang, Huaye·2016·Neurobiology of Disease
DOI 10.1016/j.nbd.2016.03.022PMC PMC4930744
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Abstract

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.

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Authors
Sun, M., Asghar, S. Z., & Zhang, H.
Affiliations
Rutgers, The State University of New Jersey (US)
Corresponding author
Zhang, Huaye
ORCID
Sun, Miao
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2016-09
Volume
93
Pages
1-11
ISSN
0969-9961 (ISSN-L)
DOI
10.1016/j.nbd.2016.03.022
PMC
PMC4930744
OpenAlex
W2322035504
Cited by
26
References
9
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 1
FWCI
2.95
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neurobiology of Disease (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute of Neurological Disorders and Stroke (U24 NS072026)
  • National Institute on Aging (P30 AG19610)
  • Arizona Department of Health Services (211002)
  • Arizona Biomedical Research Commission (4001, 0011, 05-901, 1001)
  • Michael J. Fox Foundation for Parkinson's Research
  • National Institutes of Health (NS065183, NS089578)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Par3, Numb, amyloid precursor protein, APP trafficking, APP processing, amyloid-beta, Alzheimer's disease, cell polarity, endocytic adaptor proteins
MeSH terms
Alzheimer Disease, Endocytosis, Humans, Lysosomes, Membrane Proteins, Protein Processing, Post-Translational, Endosomes, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Cell Cycle Proteins, Protein Transport, Adaptor Proteins, Signal Transducing, Amyloid Precursor Protein Secretases

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