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

Nobumasa Takasugi, Runa Araya, Yuji Kamikubo, Nanaka Kaneshiro, Ryosuke Imaoka, Hao Jin, Taku Kashiyama, Yoshie Hashimoto, Masaru Kurosawa, Takashi Uehara, Nobuyuki Nukina, Takashi Sakurai

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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-car-boxyl-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.

Original languageEnglish
Article numbere0200988
JournalPloS one
Volume13
Issue number8
DOIs
Publication statusPublished - Aug 2018

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Takasugi, N., Araya, R., Kamikubo, Y., Kaneshiro, N., Imaoka, R., Jin, H., Kashiyama, T., Hashimoto, Y., Kurosawa, M., Uehara, T., Nukina, N., & Sakurai, T. (2018). TMEM30A is a candidate interacting partner for the β-carboxyl-terminal fragment of amyloid-β precursor protein in endosomes. PloS one, 13(8), [e0200988]. https://doi.org/10.1371/journal.pone.0200988