Domains of tau Protein and Interactions with Microtubules

Gustke, N.; Trinczek, B.; Biernat, J.; Mandelkow, E.-M.; Mandelkow, E.

doi:10.1021/bi00198a017

Cited by 655Alzheimer's disease research and treatmentsMicrotubule and mitosis dynamicsNeuroinflammation and Neurodegeneration Mechanisms

Domains of tau Protein and Interactions with Microtubules

Gustke, N., Trinczek, B., Biernat, J., Mandelkow, E.-M., Mandelkow, E.·1994·Biochemistry

DOI 10.1021/bi00198a017

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Abstract

The role of the neuronal microtubule-associated protein tau has been studied by generating a series of tau constructs differing in one or several of its subdomains: length and composition of the repeat domains, extensions of the repeats in the N- or C-terminal direction, constructs without repeats, assembly vs projection domain, and number of N-terminal inserts. The interaction of the mutant tau proteins with microtubules was judged by several independent methods. (i) Direct binding assays between tau and taxol-stabilized microtubules yield dissociation constants and stoichiometries. (ii) Light scattering and X-ray scattering of assembling microtubule solutions reflect the capacity of tau to promote microtubule nucleation, elongation, and bundling in bulk solution. (iii) Dark field microscopy of assembling microtubules allows one to assess the efficiency of nucleation and bundling separately. The repeat region alone, the N-terminal domains alone, or the C-terminal tail alone binds only weakly to microtubules. However, binding is strongly enhanced by combinations such as the repeat region plus one or both of the flanking regions which could be viewed as "jaws" for tau on the microtubule surface (the proline-rich domain P upstream of the repeats and the "fifth" repeat R' downstream). Such combinations make tau's binding productive in terms of microtubule assembly and stabilization, while the combination of the flanking regions without repeats binds only unproductively. Efficien…

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Tau is a microtubule-associated protein that stabilizes microtubules by interacting with tubulin heterodimers, supporting axonal structure and neuronal morphology.
“The microtubule-associated protein tau (MAPT) was first identified as a key regulator of microtubule stability and assembly [1]. Tau stabilizes microtubules by interacting with tubulin heterodimers, thereby supporting axonal structure and maintaining neuronal morphology [2–4].”
From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [2]
Tau occurs in six different isoforms in the human central nervous system.
“Tau occurs in six different isoforms in the human central nervous system13, 14.”
From Multivalent cross-linking of actin filaments and microtubules through the microtubule-associated protein Tau (2017) · cites this paper as [13]

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Authors: Gustke, N., Trinczek, B., Biernat, J., Mandelkow, E.-M., & Mandelkow, E.
Affiliations: Max Planck Unit for Structural Molecular Biology (DE)
ORCID: Biernat, J.
Venue: Biochemistry
Publisher: American Chemical Society (ACS)
Published: 1994-10-16
Volume: 33
Issue: 32
Pages: 9511-9522
ISSN: 0006-2960 (ISSN-L)
1520-4995
DOI: 10.1021/bi00198a017
OpenAlex: W2036008741
Cited by: 655
References: 4
Citations by year: 2026: 17 · 2025: 23 · 2024: 17 · 2023: 31 · 2022: 37 · 2021: 28 · 2020: 28 · 2019: 34 · 2018: 32 · 2017: 26 · 2016: 26 · 2015: 26 · 2014: 20 · 2013: 24 · 2012: 22
FWCI: 8.18
Type: journal article
Language: en
Open access: closed
Locations: Biochemistry (publishedVersion)
PubMed (publishedVersion)
Desy publication database (The Deutsches Elektronen-Synchrotron) (submittedVersion)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: tau protein, microtubule binding, microtubule-associated proteins, microtubule nucleation, microtubule bundling, tau repeat domain, proline-rich region, N-terminal domain, C-terminal tail, binding stoichiometry, tau isoforms, phosphorylation, Alzheimer's disease
MeSH terms: Amino Acid Sequence, DNA Mutational Analysis, Humans, Microscopy, Microtubules, Molecular Sequence Data, Peptide Fragments, Protein Binding, Protein Conformation, Recombinant Proteins, Scattering, Radiation, Structure-Activity Relationship, Video Recording, X-Rays, tau Proteins

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Domains of tau Protein and Interactions with Microtubules

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