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Related Experiment Video

Updated: Jun 23, 2026

Assay for Phosphorylation and Microtubule Binding Along with Localization of Tau Protein in Colorectal Cancer Cells

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Published on: October 10, 2017

Pseudohyperphosphorylation causing AD-like changes in tau has significant effects on its polymerization.

Qian Sun¹, T Chris Gamblin

¹Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045, USA.

|May 23, 2009

Summary

Hyperphosphorylated tau protein, implicated in Alzheimer's disease (AD), shows reduced microtubule binding and impaired polymerization. This pseudohyperphosphorylation may explain tau's toxicity and neurofibrillary tangle formation in AD.

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Nuclear Magnetic Resonance Spectroscopy for the Identification of Multiple Phosphorylations of Intrinsically Disordered Proteins

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Published on: December 27, 2016

Area of Science:

Neuroscience
Biochemistry
Cell Biology

Background:

Hyperphosphorylated tau protein forms paired-helical filaments (PHFs) in Alzheimer's disease (AD).
While kinases like GSK-3beta are implicated, the functional impact of tau hyperphosphorylation on microtubule interactions remains unclear.
Normal tau has 2-3 phosphates/mole, while AD tau has ~8 phosphates/mole across ~30 sites.

Purpose of the Study:

To investigate the functional consequences of tau hyperphosphorylation on microtubule binding and polymerization.
To create and analyze tau mutants mimicking hyperphosphorylation.

Main Methods:

Generated pseudohyperphosphorylation mutants of tau via amino acid substitution at multiple sites.
Assessed microtubule binding affinity and polymerization rates of wild-type and mutant tau proteins.
Utilized sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to analyze protein migration.

Main Results:

Pseudophosphorylation of tau decreased its affinity for microtubules.
Pseudohyperphosphorylated tau showed reduced, but not significantly decreased, microtubule binding compared to single/double mutants.
Altered SDS-PAGE migration in three pseudohyperphosphorylated tau forms indicated slower nucleation and elongation rates in polymerization.

Conclusions:

Decreased microtubule affinity and impaired polymerization of pseudohyperphosphorylated tau suggest a mechanism for increased cytotoxicity in Alzheimer's disease.
These findings may also elucidate the role of tau polymerization and neurofibrillary tangle (NFT) formation in AD pathogenesis.