TMEM30A is a candidate interacting partner for the β-carboxyl-terminal fragment of amyloid-β precursor protein in endosomes

Although the aggregation of amyloid-β peptide (Aβ) clearly plays a central role in the pathogenesis of Alzheimer's disease (AD), endosomal traffic dysfunction is considered to precede Aβ aggregation and trigger AD pathogenesis. A body of evidence suggests that the β-carboxyl-terminal fragment (...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2018-08, Vol.13 (8), p.e0200988-e0200988
Main Authors: Takasugi, Nobumasa, Araya, Runa, Kamikubo, Yuji, Kaneshiro, Nanaka, Imaoka, Ryosuke, Jin, Hao, Kashiyama, Taku, Hashimoto, Yoshie, Kurosawa, Masaru, Uehara, Takashi, Nukina, Nobuyuki, Sakurai, Takashi
Format: Article
Language:English
Subjects:
Abnormalities
Agglomeration
Alzheimer's disease
Amyloid precursor protein
Biology and Life Sciences
Brain
Cell adhesion & migration
Chemistry
Cloning
Dentistry
Down syndrome
Endosomes
Hypotheses
Immunoglobulins
Impairment
Laboratories
Lipids
Localization
Medicine
Medicine and Health Sciences
Neurodegeneration
Neuropathology
Pathogenesis
Pathology
Peptides
Pharmaceutical sciences
Pharmacology
Phospholipids
Precursors
Protein transport
Proteins
Research and Analysis Methods
Traffic
Tragedies
University graduates
β-Amyloid
β-Site APP-cleaving enzyme 1
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Although the aggregation of amyloid-β peptide (Aβ) clearly plays a central role in the pathogenesis of Alzheimer's disease (AD), endosomal traffic dysfunction is considered to precede Aβ aggregation and trigger AD pathogenesis. A body of evidence suggests that the β-carboxyl-terminal fragment (βCTF) of amyloid-β precursor protein (APP), which is the direct precursor of Aβ, accumulates in endosomes and causes vesicular traffic impairment. However, the mechanism underlying this impairment remains unclear. Here we identified TMEM30A as a candidate partner for βCTF. TMEM30A is a subcomponent of lipid flippase that translocates phospholipids from the outer to the inner leaflet of the lipid bilayer. TMEM30A physically interacts with βCTF in endosomes and may impair vesicular traffic, leading to abnormally enlarged endosomes. APP traffic is also concomitantly impaired, resulting in the accumulation of APP-CTFs, including βCTF. In addition, we found that expressed BACE1 accumulated in enlarged endosomes and increased Aβ production. Our data suggested that TMEM30A is involved in βCTF-dependent endosome abnormalities that are related to Aβ overproduction.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0200988