1. Amyloid-beta oligomers increase the localization of prion protein at the cell surface.
- Author
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Caetano FA, Beraldo FH, Hajj GN, Guimaraes AL, Jürgensen S, Wasilewska-Sampaio AP, Hirata PH, Souza I, Machado CF, Wong DY, De Felice FG, Ferreira ST, Prado VF, Rylett RJ, Martins VR, and Prado MA
- Subjects
- Analysis of Variance, Animals, Biotinylation methods, Cell Membrane drug effects, Cells, Cultured, Embryo, Mammalian, Flow Cytometry methods, Green Fluorescent Proteins genetics, Hippocampus cytology, Humans, Mice, Microscopy, Confocal methods, Mitogen-Activated Protein Kinase 3 metabolism, Neurons cytology, Protein Transport drug effects, Time Factors, Transfection, rab5 GTP-Binding Proteins metabolism, Amyloid beta-Peptides pharmacology, Cell Membrane metabolism, Neurons drug effects, Peptide Fragments pharmacology, PrPC Proteins metabolism
- Abstract
In Alzheimer's disease, the amyloid-β peptide (Aβ) interacts with distinct proteins at the cell surface to interfere with synaptic communication. Recent data have implicated the prion protein (PrP(C)) as a putative receptor for Aβ. We show here that Aβ oligomers signal in cells in a PrP(C)-dependent manner, as might be expected if Aβ oligomers use PrP(C) as a receptor. Immunofluorescence, flow cytometry and cell surface protein biotinylation experiments indicated that treatment with Aβ oligomers, but not monomers, increased the localization of PrP(C) at the cell surface in cell lines. These results were reproduced in hippocampal neuronal cultures by labeling cell surface PrP(C). In order to understand possible mechanisms involved with this effect of Aβ oligomers, we used live cell confocal and total internal reflection microscopy in cell lines. Aβ oligomers inhibited the constitutive endocytosis of PrP(C), but we also found that after Aβ oligomer-treatment PrP(C) formed more clusters at the cell surface, suggesting the possibility of multiple effects of Aβ oligomers. Our experiments show for the first time that Aβ oligomers signal in a PrP(C)-dependent way and that they can affect PrP(C) trafficking, increasing its localization at the cell surface., (© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.)
- Published
- 2011
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