Journal Article

DZNE-2020-02946

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Retromer regulates postendocytic sorting of β-secretase in polarized Madin-Darby canine kidney cells.

Cuartero, Y. ; Mellado, M. ; Capell, A.DZNE* ; Alvarez-Dolado, M. ; Verges, M. (Corresponding author)

2012
Wiley-Blackwell Oxford

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Please use a persistent id in citations: doi:10.1111/j.1600-0854.2012.01392.x

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.

Keyword(s): Amyloid Precursor Protein Secretases: chemistry (MeSH) ; Amyloid Precursor Protein Secretases: genetics (MeSH) ; Amyloid Precursor Protein Secretases: metabolism (MeSH) ; Amyloid beta-Protein Precursor: metabolism (MeSH) ; Animals (MeSH) ; Cell Line (MeSH) ; Dogs (MeSH) ; Endocytosis (MeSH) ; Endosomes: metabolism (MeSH) ; Golgi Apparatus: metabolism (MeSH) ; Madin Darby Canine Kidney Cells (MeSH) ; Mice (MeSH) ; Multiprotein Complexes: metabolism (MeSH) ; Mutation (MeSH) ; Protein Interaction Domains and Motifs (MeSH) ; Protein Transport (MeSH) ; Vesicular Transport Proteins: metabolism (MeSH) ; Amyloid beta-Protein Precursor ; Multiprotein Complexes ; Vesicular Transport Proteins ; Amyloid Precursor Protein Secretases

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Contributing Institute(s):

1. Ext Ludwig-Maximilians-University (Ext LMU)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2012

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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