title: β-Amyloid precursor protein does not possess ferroxidase activity but does stabilize the cell surface ferrous iron exporter ferroportin.
abstract: Ceruloplasmin is a ferroxidase that interacts with ferroportin to export cellular iron, but is not expressed in neurons. We recently reported that the amyloid precursor protein (APP) is the analogous iron-exporting chaperone for neurons and other cells. The ferroxidase activity of APP has since been called into question. Using a triplex Fe2+ oxidation assay, we analyzed the activity of a soluble form of APP (sAPPα) within a buffer of physiological pH and anionic charge, and determined that iron oxidation originated from phosphate. Using various techniques such as flow-cytometry to measure surface presented proteins, we confirmed that endogenous APP is essential for ferroportin persistence on the neuronal surface. Therefore, despite lacking ferroxidase activity, APP still supports iron export from neurons.
authors.affiliation: Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Bruce X
authors.initials: BX
authors.lastname: Wong
authors.affiliation: School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Tsatsanis
authors.affiliation: Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia; Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Linh Q
authors.initials: LQ
authors.lastname: Lim
authors.affiliation: Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia; Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Adlard
authors.affiliation: Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia; Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.affiliation: Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, United Kingdom; Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: James A
authors.initials: JA
authors.lastname: Duce
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism*; D002570:Ceruloplasmin / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D010084:Oxidation-Reduction; D000098742:Ferroportin
chemical_list: D016564:Amyloid beta-Protein Precursor; D027682:Cation Transport Proteins; D000098742:Ferroportin; D002570:Ceruloplasmin