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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
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Caetano, Fabiana A. [1, 2, 3] ; Beraldo, Flavio H. [1, 4] ; 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 [4, 1] ; Martins, Vilma R. [5] ; Prado, Marco A. M. [4, 1, 2]
Número total de Autores: 16
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 7
Tipo de documento: Artigo Científico
Fonte: Journal of Neurochemistry; v. 117, n. 3, p. 538-553, MAY 2011.
Citações Web of Science: 52
Resumo

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)

Processo FAPESP: 09/14027-2 - Mecanismos associados à função da proteína prion e seu ligante STI1/Hop: abordagens terapêuticas
Beneficiário:Vilma Regina Martins
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 08/00390-5 - O papel da proteína prion celular no controle da diferenciação e sobrevivência celular: controle da síntese de proteínas
Beneficiário:Glaucia Noeli Maroso Hajj
Linha de fomento: Auxílio à Pesquisa - Regular