Tau protein binds to microtubules through a flexible array of distributed weak sites.
Open accessAbstract
Tau protein plays a role in the extension and maintenance of neuronal processes through a direct association with microtubules. To characterize the nature of this association, we have synthesized a collection of tau protein fragments and studied their binding properties. The relatively weak affinity of tau protein for microtubules (approximately 10(-7) M) is concentrated in a large region containing three or four 18 amino acid repeated binding elements. These are separated by apparently flexible but less conserved linker sequences of 13-14 amino acids that do not bind. Within the repeats, the binding energy for microtubules is delocalized and derives from a series of weak interactions contributed by small groups of amino acids. These unusual characteristics suggest tau protein can assume multiple conformations and can pivot and perhaps migrate on the surface of the microtubule. The flexible structure of the tau protein binding interaction may allow it to be easily displaced from the microtubule lattice and may have important consequences for its function.
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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 [14]
The Introduction (p. 717) describes tau isolated from adult brain as six related phosphopeptides and discusses several tau isoforms. It does not establish that six distinct isoforms occur in the human central nervous system; it says phosphatase treatment reduces the number of resolvable forms to four. (LLM, conf=0.82)
Experimental — accuracy not yet measuredBinding of Tau and MAP2 to filamentous actin results in actin cross-linking and filament bundling.
“Binding of Tau and MAP2 to filamentous actin results in actin cross-linking and filament bundling5, 6, 14, 22, 40–43.”
From Multivalent cross-linking of actin filaments and microtubules through the microtubule-associated protein Tau (2017) · cites this paper as [14]
The Introduction (p. 717) discusses possible tau-mediated cross-linking and bundling of microtubules, not actin filaments. Searches for filamentous actin, actin binding, and actin bundling found no passage in our copy addressing the claimed effects of tau and MAP2 on actin. (LLM, conf=0.76)
Experimental — accuracy not yet measured
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- Authors
- Butner, K. A., & Kirschner, M. W.
- Affiliations
- University of California, San Francisco (US)
- ORCID
- Kirschner, M W
- Venue
- The Journal of cell biology
- Publisher
- Rockefeller University Press
- Published
- 1991-11-01
- Volume
- 115
- Issue
- 3
- Pages
- 717-730
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2289193
- OpenAlex
- W2127229268
- Cited by
- 550
- References
- 6
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 14 · 2023: 13 · 2022: 9 · 2021: 15 · 2020: 18 · 2019: 22 · 2018: 23 · 2017: 16 · 2016: 22 · 2015: 22 · 2014: 21 · 2013: 12 · 2012: 18
- FWCI
- 13.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM 26875)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- tau protein, microtubule binding, microtubule-associated proteins, binding sites, linker sequence, protein conformation, neural processes, binding affinity, protein-microtubule interaction
- MeSH terms
- Amino Acid Sequence, Animals, Binding Sites, Brain, Cattle, Kinetics, Microtubules, Models, Structural, Molecular Sequence Data, Oligonucleotides, Plasmids, Protein Conformation, Recombinant Proteins, Repetitive Sequences, Nucleic Acid, RNA, Messenger, Thermodynamics, Transcription, Genetic, Tubulin, tau Proteins
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