TY  - JOUR
AU  - Cuartero, Yasmina
AU  - Mellado, Maravillas
AU  - Capell, Anja
AU  - Alvarez-Dolado, Manuel
AU  - Verges, Marcel
TI  - Retromer regulates postendocytic sorting of β-secretase in polarized Madin-Darby canine kidney cells.
JO  - Traffic
VL  - 13
IS  - 10
SN  - 1398-9219
CY  - Oxford
PB  - Wiley-Blackwell
M1  - DZNE-2020-02946
SP  - 1393-1410
PY  - 2012
AB  - 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.
KW  - Amyloid Precursor Protein Secretases: chemistry
KW  - Amyloid Precursor Protein Secretases: genetics
KW  - Amyloid Precursor Protein Secretases: metabolism
KW  - Amyloid beta-Protein Precursor: metabolism
KW  - Animals
KW  - Cell Line
KW  - Dogs
KW  - Endocytosis
KW  - Endosomes: metabolism
KW  - Golgi Apparatus: metabolism
KW  - Madin Darby Canine Kidney Cells
KW  - Mice
KW  - Multiprotein Complexes: metabolism
KW  - Mutation
KW  - Protein Interaction Domains and Motifs
KW  - Protein Transport
KW  - Vesicular Transport Proteins: metabolism
KW  - Amyloid beta-Protein Precursor (NLM Chemicals)
KW  - Multiprotein Complexes (NLM Chemicals)
KW  - Vesicular Transport Proteins (NLM Chemicals)
KW  - Amyloid Precursor Protein Secretases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:22758778
DO  - DOI:10.1111/j.1600-0854.2012.01392.x
UR  - https://pub.dzne.de/record/136624
ER  -