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Interaction of Tau with Fe65 links tau to APP

Christian Barbato1, Nadia Canu, Nicola Zambrano

  • 1Dipartimento di Neuroscienze, Università di Roma Tor Vergata, Via Montpellier 1, 00133 Roma, Italy.

Neurobiology of Disease
|February 3, 2005
PubMed

Insights

Fe65 protein links Alzheimer's disease (AD) proteins APP and Tau. This interaction, crucial for AD pathogenesis, is regulated by Tau phosphorylation and requires an intact microtubule network.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Alzheimer's disease (AD) pathogenesis involves beta-amyloid precursor protein (APP) and Tau.
  • Molecular links between APP and Tau in AD remain unclear.

Purpose of the Study:

  • Investigate the molecular mechanisms linking APP and Tau.
  • Determine if Fe65, an APP-binding protein, interacts with Tau.

Main Methods:

  • Co-immunoprecipitation and co-localization assays to detect protein interactions.
  • Förster Resonance Energy Transfer (FRET) to confirm in vivo association.
  • Deletion studies to identify interaction domains.
  • Analysis of Tau phosphorylation by GSK3beta and Cdk5.
  • Laser scanner microscopy to visualize protein complexes.

Main Results:

  • Fe65 associates with Tau both in vivo and in vitro.
  • The N-terminal domain of Tau and the PTB1 domain of Fe65 are essential for this interaction.
  • Tau phosphorylation by GSK3beta and Cdk5 regulates Fe65-Tau binding.
  • An intact microtubule network is required for the interaction.
  • Preliminary evidence suggests complexes involving Tau, Fe65, and APP.

Conclusions:

  • Fe65 acts as a molecular bridge between APP and Tau.
  • This Fe65-mediated interaction is a potential therapeutic target for Alzheimer's disease.
  • Findings reveal novel crosstalk between key AD-related proteins.

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