| First Author | Takasugi N | Year | 2018 |
| Journal | PLoS One | Volume | 13 |
| Issue | 8 | Pages | e0200988 |
| PubMed ID | 30086173 | Mgi Jnum | J:273543 |
| Mgi Id | MGI:6294211 | Doi | 10.1371/journal.pone.0200988 |
| Citation | Takasugi N, et al. (2018) TMEM30A is a candidate interacting partner for the beta-carboxyl-terminal fragment of amyloid-beta precursor protein in endosomes. PLoS One 13(8):e0200988 |
| abstractText | Although the aggregation of amyloid-beta peptide (Abeta) clearly plays a central role in the pathogenesis of Alzheimer's disease (AD), endosomal traffic dysfunction is considered to precede Abeta aggregation and trigger AD pathogenesis. A body of evidence suggests that the beta-carboxyl-terminal fragment (betaCTF) of amyloid-beta precursor protein (APP), which is the direct precursor of Abeta, 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 betaCTF. 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 betaCTF 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 betaCTF. In addition, we found that expressed BACE1 accumulated in enlarged endosomes and increased Abeta production. Our data suggested that TMEM30A is involved in betaCTF-dependent endosome abnormalities that are related to Abeta overproduction. |
