title: Copper promotes the trafficking of the amyloid precursor protein.
abstract: Accumulation of the amyloid β peptide in the cortical and hippocampal regions of the brain is a major pathological feature of Alzheimer disease. Amyloid β peptide is generated from the sequential protease cleavage of the amyloid precursor protein (APP). We reported previously that copper increases the level of APP at the cell surface. Here we report that copper, but not iron or zinc, promotes APP trafficking in cultured polarized epithelial cells and neuronal cells. In SH-SY5Y neuronal cells and primary cortical neurons, copper promoted a redistribution of APP from a perinuclear localization to a wider distribution, including neurites. Importantly, a change in APP localization was not attributed to an up-regulation of APP protein synthesis. Using live cell imaging and endocytosis assays, we found that copper promotes an increase in cell surface APP by increasing its exocytosis and reducing its endocytosis, respectively. This study identifies a novel mechanism by which copper regulates the localization and presumably the function of APP, which is of major significance for understanding the role of APP in copper homeostasis and the role of copper in Alzheimer disease.
authors.affiliation: From the Department of Genetics.
authors.forename: Karla M
authors.initials: KM
authors.lastname: Acevedo
authors.affiliation: the Centre for Neuroscience, and; the Mental Health Research Institute, University of Melbourne, Melbourne, Victoria 3010, Australia and.
authors.forename: Ya Hui
authors.initials: YH
authors.lastname: Hung
authors.affiliation: From the Department of Genetics.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Dalziel
authors.affiliation: the Mental Health Research Institute, University of Melbourne, Melbourne, Victoria 3010, Australia and; the Department of Pathology.
authors.forename: Qiao-Xin
authors.initials: QX
authors.lastname: Li
authors.affiliation: the Mental Health Research Institute, University of Melbourne, Melbourne, Victoria 3010, Australia and; the Department of Pathology.
authors.forename: Katrina
authors.initials: K
authors.lastname: Laughton
authors.affiliation: the Mental Health Research Institute, University of Melbourne, Melbourne, Victoria 3010, Australia and.
authors.forename: Krutika
authors.initials: K
authors.lastname: Wikhe
authors.affiliation: the Mental Health Research Institute, University of Melbourne, Melbourne, Victoria 3010, Australia and; Commonwealth Scientific and Research Organization (CSIRO) Molecular and Health Technologies, Parkville, Victoria 3052, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Rembach
authors.affiliation: the Mental Health Research Institute, University of Melbourne, Melbourne, Victoria 3010, Australia and.
authors.forename: Blaine
authors.initials: B
authors.lastname: Roberts
authors.affiliation: the Centre for Neuroscience, and; the Mental Health Research Institute, University of Melbourne, Melbourne, Victoria 3010, Australia and.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.affiliation: the Mental Health Research Institute, University of Melbourne, Melbourne, Victoria 3010, Australia and.
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.affiliation: From the Department of Genetics,. Electronic address: j.camakaris@unimelb.edu.au.
authors.forename: James
authors.initials: J
authors.lastname: Camakaris
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D003300:Copper / Q000378:metabolism* / Q000494:pharmacology; D004285:Dogs; D004705:Endocytosis / Q000187:drug effects / Q000235:genetics; D006801:Humans; D016501:Neurites / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D003300:Copper