Aβ modulates actin cytoskeleton via SHIP2-mediated phosphoinositide metabolism.

ABSTRACT: Emerging evidences suggest that phospholipid metabolism is altered in Alzheimer's disease (AD), but molecular mechanisms on how this affects neurodegeneration in AD is poorly understood. SHIP2 is a phosphoinositide-metabolizing enzyme, which dephosphorylates PI(3,4,5)P₃ resulting to PI(3,4)P₂, and it has been recently shown that Aβ directly increases the activity of SHIP2. Here we monitored, utilizing fluorescent SHIP2 biosensor, real-time increase of PI(3,4)P₂-containing vesicles in HT22 cells treated with Aβ. Interestingly, PI(3,4)P₂ is accumulated at late endosomes and lysosomal vesicles. We further discovered that ARAP3 can be attracted to PI(3,4)P₂-positive mature endosomes via its PH domain and this facilitates the degradation of

SUBMITTER: Lee HN 

PROVIDER: S-EPMC6820556 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature