Tau phosphorylation by cdk5 and Fyn in response to amyloid peptide Aβ25-35: Involvement of lipid rafts

Paula Hernandez, Gloria Lee, Marcela Sjoberg, Ricardo B. MacCioni

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Alzheimer's disease (AD) is characterized by the accumulation of protein filaments, namely extracellular amyloid-β (Aβ) 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 GSK3β. In addition, tau hyperphosphorylation also occurs at Tyr residues. To find a link between Aβ and tau phosphorylation, we investigated the effects of short-term Aβ 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 Aβ-induced signaling cascades. After 2 min of Aβ 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 Aβ-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 Aβ-promoted early events involving tau hyperphosphorylation, and their possible implications for AD pathogenesis.

Original languageEnglish (US)
Pages (from-to)149-156
Number of pages8
JournalJournal of Alzheimer's Disease
Volume16
Issue number1
DOIs
StatePublished - 2009
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Amyloid-β
  • Cdk5
  • Fyn
  • Lipid rafts
  • Neuronal membrane
  • Tau phosphorylation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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