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@ARTICLE{Cuartero:136624,
author = {Cuartero, Yasmina and Mellado, Maravillas and Capell, Anja
and Alvarez-Dolado, Manuel and Verges, Marcel},
title = {{R}etromer regulates postendocytic sorting of β-secretase
in polarized {M}adin-{D}arby canine kidney cells.},
journal = {Traffic},
volume = {13},
number = {10},
issn = {1398-9219},
address = {Oxford},
publisher = {Wiley-Blackwell},
reportid = {DZNE-2020-02946},
pages = {1393-1410},
year = {2012},
abstract = {β-Amyloid (Aβ) peptides are generated from the successive
proteolytic processing of the amyloid precursor protein
(APP) by the β-APP cleaving enzyme (BACE or β-secretase)
and the γ-secretase complex. Initial cleavage of APP by
BACE leads into the amyloidogenic pathway, causing or
exacerbating Alzheimer's disease. Therefore, their
intracellular traffic can determine how easily and
frequently BACE has access to and cleaves APP. Here, we have
used polarized Madin-Darby canine kidney (MDCK) cells stably
expressing APP and BACE to examine the regulation of their
polarized trafficking by retromer, a protein complex
previously implicated in their endosome-to-Golgi transport.
Our data show that retromer interacts with BACE and
regulates its postendocytic sorting in polarized MDCK cells.
Depleting retromer, inhibiting retromer function, or
preventing BACE interaction with retromer, alters
trafficking of BACE, which thereby increases its
localization in the early endocytic compartment. As a
result, this slows endocytosis of apically localized BACE,
promoting its recycling and apical-to-basolateral
transcytosis, which increases APP/BACE interaction and
subsequent cleavage of APP toward generation and secretion
of Aβ peptides.},
keywords = {Amyloid Precursor Protein Secretases: chemistry / Amyloid
Precursor Protein Secretases: genetics / Amyloid Precursor
Protein Secretases: metabolism / Amyloid beta-Protein
Precursor: metabolism / Animals / Cell Line / Dogs /
Endocytosis / Endosomes: metabolism / Golgi Apparatus:
metabolism / Madin Darby Canine Kidney Cells / Mice /
Multiprotein Complexes: metabolism / Mutation / Protein
Interaction Domains and Motifs / Protein Transport /
Vesicular Transport Proteins: metabolism / Amyloid
beta-Protein Precursor (NLM Chemicals) / Multiprotein
Complexes (NLM Chemicals) / Vesicular Transport Proteins
(NLM Chemicals) / Amyloid Precursor Protein Secretases (NLM
Chemicals)},
cin = {Ext LMU},
ddc = {570},
cid = {I:(DE-2719)5000048},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:22758778},
doi = {10.1111/j.1600-0854.2012.01392.x},
url = {https://pub.dzne.de/record/136624},
}