Tau Phosphorylation by cdk5 and Fyn in Response to Amyloid Peptide A beta(25-35): Involvement of Lipid Rafts

Hernández P; Lee G.; Sjoberg, M; Maccioni, RB

Abstract

Alzheimer's disease (AD) is characterized by the accumulation of protein filaments, namely extracellular amyloid-ß (Aß) fibrils and intracellular neurofibrillary tangles, which are composed of aggregated hyperphosphorylated tau. Tau hyperphosphorylation is the product of deregulated Ser/Thr kinases such as cdk5 and GSK3ß. In addition, tau hyperphosphorylation also occurs at Tyr residues. To find a link between Aß and tau phosphorylation, we investigated the effects of short-term Aß treatments on SHSY-5Y cells. We analyzed phosphorylated tau variants in lipid rafts and the possible role of Tyr18 and Ser396/404 tau phosphorylation in Aß-induced signaling cascades. After 2 min of Aß treatment, phospho-Tyr18-tau and its association with rafts increased. Phospho-Ser 396/404-tau became detectable in rafts after 10 min treatment, which temporally correlated with the detection of cdk5 and p35 activator in lipid rafts. To determine the role of cdk5 in tau phosphorylation at Ser396/404 in lipid rafts, we pre-incubated cells with cdk5 inhibitor roscovitine, and observed that the Aß-induced tau phosphorylation at Ser 396/404 in rafts was abolished as well as cdk5/p35 association with rafts. These data suggest a role for cdk5 in the Aß-promoted early events involving tau hyperphosphorylation, and their possible implications for AD pathogenesis. © 2009 - IOS Press and the authors. All rights reserved.

Más información

Título según WOS: Tau Phosphorylation by cdk5 and Fyn in Response to Amyloid Peptide A beta(25-35): Involvement of Lipid Rafts
Título según SCOPUS: Tau phosphorylation by cdk5 and Fyn in response to amyloid peptide A?25-35: Involvement of lipid rafts
Título de la Revista: JOURNAL OF ALZHEIMERS DISEASE
Volumen: 16
Número: 1
Editorial: IOS Press
Fecha de publicación: 2009
Página de inicio: 149
Página final: 156
Idioma: English
DOI:

10.3233/JAD-2009-0933

Notas: ISI, SCOPUS