Post Translational Modulation of β-Amyloid Precursor Protein Trafficking to the Cell Surface Alters Neuronal Iron Homeostasis.

Post Translational Modulation of β-Amyloid Precursor Protein Trafficking to the Cell Surface Alters Neuronal Iron Homeostasis.
Neurochem Res. 2019 Feb 22;:
Authors: Tsatsanis A, Dickens S, Kwok JCF, Wong BX, Duce JA
Abstract
Cell surface β-Amyloid precursor protein (APP) is known to have a functional role in iron homeostasis through stabilising the iron export protein ferroportin (FPN). Mechanistic evidence of this role has previously only been provided through transcriptional or translational depletion of total APP levels. However, numerous post-translational modifications of APP are reported to regulate the location and trafficking of this protein to the cell surface. Stable overexpressing cell lines were generated that overexpressed APP with disrupted N-glycosylation (APPN467K and APPN496K) or ectodomain phosphorylation (APPS206A); sites selected for their proximity to the FPN binding site on the E2 domain of APP. We hypothesise that impaired N-glycosylation or phosphorylation of APP disrupts the functional location on the cell surface or binding to FPN to consequentially alter intracellular iron levels through impaired cell surface FPN stability. Outcomes confirm that these post-translational modifications are essential for the correct location of APP on the cell surface and highlight a novel mechanism by which the cell can modulate iron homeostasis. Further interrogation of other post-translational processes to APP is warrante...

Source: Neurochemical Research - February 22, 2019 Category: Neuroscience Authors: Tsatsanis A, Dickens S, Kwok JCF, Wong BX, Duce JA Tags: Neurochem Res Source Type: research