Copper promotes the trafficking of the amyloid precursor protein.
J Biol Chem
; 286(10): 8252-8262, 2011 Mar 11.
Article
em En
| MEDLINE
| ID: mdl-21177866
ABSTRACT
Accumulation of the amyloid ß peptide in the cortical and hippocampal regions of the brain is a major pathological feature of Alzheimer disease. Amyloid ß 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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neuritos
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Precursor de Proteína beta-Amiloide
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Cobre
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Doença de Alzheimer
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2011
Tipo de documento:
Article