What question did this study set out to answer?

To resolve discrepancies in Tau-microtubule binding affinities by characterizing the interaction across a wide concentration range.

September 1, 2000Journal of Biological ChemistryOpen Access

Nonsaturable Binding Indicates Clustering of Tau on the Microtubule Surface in a Paired Helical Filament-like Conformation

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To resolve discrepancies in Tau-microtubule binding affinities by characterizing the interaction across a wide concentration range.
Determined binding affinities across broad concentration ranges using a sensitive enzyme-linked immunosorbent assay (ELISA).
Evaluated the regulatory impacts of Tau isoforms, phosphorylation status, and dimerization on binding phases.
Monitored conformational changes and aggregation into paired helical filament-like structures using thioflavin S fluorescence.
Tau-microtubule binding is biphasic, featuring a saturable primary phase (dissociation constant ~0.1 µM; stoichiometry ~0.2 Tau per tubulin dimer) and an unexpected nonsaturable second phase at free Tau concentrations exceeding 2 µM.
The secondary overloading phase displayed a linear increase in bound Tau proportional to microtubule concentration, characterized by an overloading parameter of approximately 50 µM.
Overloading Tau on microtubules triggered marked increases in thioflavin S fluorescence, indicating that paired helical filament-like conformational changes can initiate directly along polyanionic microtubule surfaces.

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Implication

In vitro binding assay demonstrates biphasic, nonsaturable Tau clustering on microtubules, suggesting that early Alzheimer paired helical filament assembly occurs directly on the microtubule surface.

Cite This Study

Ackmann et al. (2000) studied this question.

synapsesocial.com/papers/69dbf1389e6f14d6f1684e85 https://doi.org/10.1074/jbc.m002590200

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Implication

In vitro binding assay demonstrates biphasic, nonsaturable Tau clustering on microtubules, suggesting that early Alzheimer paired helical filament assembly occurs directly on the microtubule surface.

Nonsaturable Binding Indicates Clustering of Tau on the Microtubule Surface in a Paired Helical Filament-like Conformation

Key Points

Discussion

Implication

Cite This Study

Nonsaturable Binding Indicates Clustering of Tau on the Microtubule Surface in a Paired Helical Filament-like Conformation

Key Points

Discussion

Implication

Cite This Study

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