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Disulfide-cross-linked tau and MAP2 homodimers readily promote microtubule assembly

L Di Noto1, M A DeTure, D L Purich

  • 1Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Health Science Center, Gainesville 32610-0245, USA.

Molecular Cell Biology Research Communications : MCBRC
|November 30, 1999
PubMed

Insights

Disulfide cross-linking into homodimers does not drive filament formation in Alzheimer's disease. Tau and MAP2 dimers bind microtubules similarly to monomers, challenging previous hypotheses.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Cell Biology

Background:

  • Neuronal proteins Tau and MAP2 bind microtubules and actin filaments via homologous C-terminal MT-binding regions (MTBRs).
  • Tau-MTBR is a key component of Alzheimer's paired helical filaments, and both Tau and MAP2 form filaments in vitro from disulfide-linked homodimers.

Purpose of the Study:

  • To investigate whether disulfide formation blocks Tau-Tau or MAP2-MAP2 dimer binding to microtubules.
  • To determine if this blockage diverts dimers toward filament formation, a potential driver in Alzheimer's disease.

Main Methods:

  • Comparative analysis of microtubule binding affinity for monomeric and disulfide-linked homodimeric forms of Tau and MAP2.
  • Assessment of the ability of cross-linked homodimers to promote tubulin polymerization.

Main Results:

  • Cross-linked Tau and MAP2 homodimers readily promote tubulin polymerization.
  • The affinity of both monomer and dimer forms for microtubules was found to be surprisingly similar.

Conclusions:

  • Disulfide cross-bridging into homodimers is unlikely to be the primary driving force for filament formation in Alzheimer's disease.
  • The similar binding affinities suggest alternative mechanisms may be responsible for Tau filament aggregation in Alzheimer's pathology.

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