Caetano F.A.,University of Western Ontario |
Caetano F.A.,Federal University of Minas Gerais |
Beraldo F.H.,University of Western Ontario |
Hajj G.N.M.,International Center for Research and Education Antonio Prudente Foundation |
And 15 more authors.
Journal of Neurochemistry | Year: 2011
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 (PrPC) as a putative receptor for Aβ. We show here that Aβ oligomers signal in cells in a PrPC-dependent manner, as might be expected if Aβ oligomers use PrPC 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 PrPC at the cell surface in cell lines. These results were reproduced in hippocampal neuronal cultures by labeling cell surface PrPC. 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 PrPC-dependent way and that they can affect PrPC trafficking, increasing its localization at the cell surface. © 2011 International Society for Neurochemistry.