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

Neurochemical Research
Andrew TsatsanisJames A Duce

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 warranted in order to ful...Continue Reading

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Citations

Sep 4, 2020·Experimental Biology and Medicine·Santosh R D'Mello, Mark C Kindy
Jan 1, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wenyue WangZhicheng Xiao
Jun 16, 2019·The Journal of Biological Chemistry·Debomoy K LahiriRuizhi Wang
Jan 2, 2020·International Journal of Molecular Sciences·Tao ZhangTae Ho Lee
Aug 21, 2020·Learning & Memory·Jack T Rogers, Catherine M Cahill
Feb 18, 2020·Frontiers in Neuroscience·Nao Yan, JunJian Zhang
Nov 22, 2020·The Journal of Biological Chemistry·Peng LeiAshley I Bush
Jan 10, 2021·Antioxidants·Pamela J UrrutiaMarco Tulio Núñez
Jul 30, 2020·Progress in Neurobiology·Laura Mahoney-SánchezJean-Christophe Devedjian
Sep 24, 2021·Journal of Neurochemistry·Md JakariaScott Ayton

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Methods Mentioned

BETA
glycosylation
gylcosylation
flow cytometry
Fluorescence

Software Mentioned

FlowJo
Image J

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