Amyloid-beta oligomers increase the localization of prion protein at the cell surface

Author(s):Show less -

Caetano, Fabiana A. ^{[1, 2, 3]} ; Beraldo, Flavio H. ^{[4, 1]} ; Hajj, Glaucia N. M. ^[5] ; Guimaraes, Andre L. ^{[4, 1, 6]} ; Juergensen, Sofia ^{[7, 3]} ; Wasilewska-Sampaio, Ana Paula ^[5] ; Hirata, Pedro H. F. ^[5] ; Souza, Ivana ^{[1, 2, 3]} ; Machado, Cleiton F. ^[5] ; Wong, Daisy Y. -L. ^[1] ; De Felice, Fernanda G. ^{[7, 3]} ; Ferreira, Sergio T. ^{[7, 3]} ; Prado, Vania F. ^{[4, 1, 2]} ; Rylett, R. Jane ^{[1, 4]} ; Martins, Vilma R. ^[5] ; Prado, Marco A. M. ^{[4, 1, 2]}

Affiliation

^[1] Univ Western Ontario, Robarts Res Inst, J Allyn Taylor Ctr Cell Biol, Mol Brain Res Grp, London, ON N6A 5K8 - Canada

^[2] Univ Western Ontario, Dept Anat & Cell Biol, London, ON - Canada

^[3] Univ Fed Minas Gerais, Fac Med, Program Mol Pharmacol, Belo Horizonte, MG - Brazil

^[4] Univ Western Ontario, Dept Physiol & Pharmacol, London, ON - Canada

^[5] AC Camargo Hosp, Int Ctr Res & Educ, Antonio Prudente Fdn, Sao Paulo - Brazil

^[6] Univ Estadual Montes Claros, Dept Dent, Montes Claros, MG - Brazil

^[7] Univ Fed Rio de Janeiro, Inst Med Biochem, Rio De Janeiro - Brazil

• Document type: Journal article
• Source: Journal of Neurochemistry; v. 117, n. 3, p. 538-553, MAY 2011.
• Web of Science Citations: 52

Abstract

P>In Alzheimer's disease, the amyloid-beta peptide (A beta) 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 A beta. We show here that A beta oligomers signal in cells in a PrP(C)-dependent manner, as might be expected if A beta oligomers use PrP(C) as a receptor. Immunofluorescence, flow cytometry and cell surface protein biotinylation experiments indicated that treatment with A beta 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 A beta oligomers, we used live cell confocal and total internal reflection microscopy in cell lines. A beta oligomers inhibited the constitutive endocytosis of PrP(C), but we also found that after A beta oligomer-treatment PrP(C) formed more clusters at the cell surface, suggesting the possibility of multiple effects of A beta oligomers. Our experiments show for the first time that A beta oligomers signal in a PrP(C)-dependent way and that they can affect PrP(C) trafficking, increasing its localization at the cell surface. (AU)

• FAPESP's process: 08/00390-5 - Cellular prion protein in cell differentiation and protection: control of protein synthesis
• Grantee: Glaucia Noeli Maroso Hajj
• Support type: Regular Research Grants
• FAPESP's process: 09/14027-2 - Mechanisms associated with the function of prion protein and its ligand STI1/Hop: therapeutic approaches
• Grantee: Vilma Regina Martins
• Support type: Research Projects - Thematic Grants