Local Nucleation of Microtubule Bundles through Tubulin Concentration into a Condensed Tau Phase
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Abstract
Non-centrosomal microtubule bundles play important roles in cellular organization and function. Although many diverse proteins are known that can bundle microtubules, biochemical mechanisms by which cells could locally control the nucleation and formation of microtubule bundles are understudied. Here, we demonstrate that the concentration of tubulin into a condensed, liquid-like compartment composed of the unstructured neuronal protein tau is sufficient to nucleate microtubule bundles. We show that, under conditions of macro-molecular crowding, tau forms liquid-like drops. Tubulin partitions into these drops, efficiently increasing tubulin concentration and driving the nucleation of microtubules. These growing microtubules form bundles, which deform the drops while remaining enclosed by diffusible tau molecules exhibiting a liquid-like behavior. Our data suggest that condensed compartments of microtubule bundling proteins could promote the local formation of microtubule bundles in neurons by acting as non-centrosomal microtubule nucleation centers and that liquid-like tau encapsulation could provide both stability and plasticity to long axonal microtubule bundles.
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Tau is able to form liquid droplets, which act as sites to recruit and nucleate tubulin into microtubule bundles.
“Tau is able to form liquid droplets, which act as sites to recruit and nucleate tubulin into microtubule bundles [224].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [224]
Tau phosphorylation at specific sites overlapping AD sites diminishes tau's affinity for microtubules.
“It is well established that tau phosphorylation, especially at specific sites that overlap with the sites that are phosphorylated in AD, diminishes the affinity of tau for microtubules (4, 26–29).”
From All the Tau We Cannot See (2023) · cites this paper as [27]
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- Authors
- Hernández-Vega, A., Braun, M., Scharrel, L., Jahnel, M., Wegmann, S., Hyman, B. T., Alberti, S., Diez, S., & Hyman, A. A.
- Affiliations
- Czech Academy of Sciences, Institute of Biotechnology (CZ)
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- Harvard University (US)
- Corresponding author
- Diez, Stefan
- Hyman, Anthony A.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 20
- Issue
- 10
- Pages
- 2304-2312
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5828996
- OpenAlex
- W2606756014
- Cited by
- 395
- References
- 61
- Citations by year
- 2026: 43 · 2025: 49 · 2024: 41 · 2023: 48 · 2022: 49 · 2021: 41 · 2020: 50 · 2019: 45 · 2018: 27 · 2017: 2
- FWCI
- 18.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- ASEP (submittedVersion, public-domain)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Max-Planck-Gesellschaft
- Bundesministerium für Bildung und Forschung (01EK1606C)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Keywords
- microtubule bundling, microtubule nucleation, tau protein, axonal microtubules, phase separation
- MeSH terms
- Animals, Cytoskeleton, Humans, Microtubules, Tubulin, tau Proteins, Protein Isoforms, Fluorescence Recovery After Photobleaching
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