title: Amyloid-beta oligomers increase the localization of prion protein at the cell surface.
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.
authors.affiliation: J. Allyn Taylor Centre for Cell Biology, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
authors.forename: Fabiana A
authors.initials: FA
authors.lastname: Caetano
authors.forename: Flavio H
authors.initials: FH
authors.lastname: Beraldo
authors.forename: Glaucia N M
authors.initials: GN
authors.lastname: Hajj
authors.forename: Andre L
authors.initials: AL
authors.lastname: Guimaraes
authors.forename: Sofia
authors.initials: S
authors.lastname: Jürgensen
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Wasilewska-Sampaio
authors.forename: Pedro H F
authors.initials: PH
authors.lastname: Hirata
authors.forename: Ivana
authors.initials: I
authors.lastname: Souza
authors.forename: Cleiton F
authors.initials: CF
authors.lastname: Machado
authors.forename: Daisy Y-L
authors.initials: DY
authors.lastname: Wong
authors.forename: Fernanda G
authors.initials: FG
authors.lastname: De Felice
authors.forename: Sergio T
authors.initials: ST
authors.lastname: Ferreira
authors.forename: Vania F
authors.initials: VF
authors.lastname: Prado
authors.forename: R Jane
authors.initials: RJ
authors.lastname: Rylett
authors.forename: Vilma R
authors.initials: VR
authors.lastname: Martins
authors.forename: Marco A M
authors.initials: MA
authors.lastname: Prado
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D019921:Biotinylation / Q000379:methods; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005434:Flow Cytometry / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D018621:PrPC Proteins / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D018621:PrPC Proteins; C075222:amyloid beta-protein (1-42); D049452:Green Fluorescent Proteins; D048052:Mitogen-Activated Protein Kinase 3; D020696:rab5 GTP-Binding Proteins