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Updated: Apr 11, 2026
Quantitative Microtubule Fractionation Technique to Separate Stable Microtubules, Labile Microtubules, and Free Tubulin in Mouse Tissues
Published on: November 17, 2023
Tau stabilizes microtubules by binding at the interface between tubulin heterodimers
Harindranath Kadavath1, Romina V Hofele1, Jacek Biernat2
1Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany;
Abstract:
The structure, dynamic behavior, and spatial organization of microtubules are regulated by microtubule-associated proteins. An important microtubule-associated protein is the protein Tau, because its microtubule interaction is impaired in the course of Alzheimer's disease and several other neurodegenerative diseases. Here, we show that Tau binds to microtubules by using small groups of evolutionary conserved residues. The binding sites are formed by residues that are essential for the pathological aggregation of Tau, suggesting competition between physiological interaction and pathogenic misfolding. Tau residues in between the microtubule-binding sites remain flexible when Tau is bound to microtubules in agreement with a highly dynamic nature of the Tau-microtubule interaction. By binding at the interface between tubulin heterodimers, Tau uses a conserved mechanism of microtubule polymerization and, thus, regulation of axonal stability and cell morphology.
Insights
The protein Tau binds to microtubules using conserved residues, revealing a competition between its normal function and pathological misfolding in neurodegenerative diseases like Alzheimer's.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Microtubule-associated proteins regulate microtubule structure and dynamics.
- The protein Tau is crucial as its microtubule interaction is impaired in Alzheimer's and other neurodegenerative diseases.
Purpose of the Study:
- To investigate the binding mechanism of Tau to microtubules.
- To explore the relationship between Tau's physiological interaction and its pathological aggregation.
Main Methods:
- Analysis of evolutionary conserved residues involved in Tau-microtubule binding.
- Assessment of Tau residue flexibility during microtubule interaction.
Main Results:
- Tau binds microtubules via small, evolutionarily conserved residue groups.
- These binding sites overlap with residues critical for Tau's pathological aggregation, suggesting functional competition.
- Tau residues between binding sites remain flexible, indicating a dynamic interaction.
Conclusions:
- Tau utilizes a conserved mechanism at the tubulin interface to regulate microtubule polymerization.
- This interaction is vital for maintaining axonal stability and cell morphology.
- Understanding this mechanism offers insights into neurodegenerative disease pathogenesis.
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