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Cited by 258Alzheimer's disease research and treatmentsCellular transport and secretionNeuroscience and Neuropharmacology Research

Sorting of the Alzheimer's Disease Amyloid Precursor Protein Mediated by the AP-4 Complex

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Burgos, Patricia V., Mardones, Gonzalo A., Rojas, Adriana L., daSilva, Luis L.P., Prabhu, Yogikala, Hurley, James H., Bonifacino, Juan S.·2010·Developmental Cell
DOI 10.1016/j.devcel.2010.01.015PMC PMC2841041
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Abstract

Adaptor protein 4 (AP-4) is the most recently discovered and least well-characterized member of the family of heterotetrameric adaptor protein (AP) complexes that mediate sorting of transmembrane cargo in post-Golgi compartments. Herein, we report the interaction of an YKFFE sequence from the cytosolic tail of the Alzheimer's disease amyloid precursor protein (APP) with the mu4 subunit of AP-4. Biochemical and X-ray crystallographic analyses reveal that the properties of the APP sequence and the location of the binding site on mu4 are distinct from those of other signal-adaptor interactions. Disruption of the APP-AP-4 interaction decreases localization of APP to endosomes and enhances gamma-secretase-catalyzed cleavage of APP to the pathogenic amyloid-beta peptide. These findings demonstrate that APP and AP-4 engage in a distinct type of signal-adaptor interaction that mediates transport of APP from the trans-Golgi network (TGN) to endosomes, thereby reducing amyloidogenic processing of the protein.

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Cited by

Sorted by citations

Authors
Burgos, P. V., Mardones, G. A., Rojas, A. L., daSilva, L. L. P., Prabhu, Y., Hurley, J. H., & Bonifacino, J. S.
Affiliations
National Institutes of Health (US)
Corresponding author
Bonifacino, Juan S.
ORCID
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2010-03
Volume
18
Issue
3
Pages
425-436
ISSN
1534-5807 (ISSN-L)
DOI
10.1016/j.devcel.2010.01.015
PMC
PMC2841041
OpenAlex
W2137575965
Cited by
258
References
2
Citations by year
2026: 7 · 2025: 8 · 2024: 11 · 2023: 8 · 2022: 17 · 2021: 9 · 2020: 18 · 2019: 16 · 2018: 14 · 2017: 13 · 2016: 15 · 2015: 24 · 2014: 21 · 2013: 24 · 2012: 28
FWCI
15.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Developmental Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
Funders
  • National Institute of General Medical Sciences (Y1-GM-1104)
  • National Cancer Institute (Y1-CO-1020)
  • U.S. Department of Energy (DE-AC02-06CH11357)
Topics
  • Health Sciences › Medicine › Physiology › 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
Alzheimer's disease, amyloid precursor protein, adaptor protein complexes, endosomal trafficking, trans-Golgi network, gamma-secretase, amyloid-beta, protein sorting
MeSH terms
Alzheimer Disease, Amino Acid Sequence, Binding Sites, HeLa Cells, Humans, Models, Molecular, Molecular Sequence Data, Endosomes, Recombinant Proteins, Signal Transduction, Amyloid beta-Protein Precursor, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Crystallography, X-Ray, Protein Subunits, Protein Transport, Adaptor Protein Complex 4, Multiprotein Complexes, Amyloid Precursor Protein Secretases, Protein Interaction Domains and Motifs, In Vitro Techniques

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