Evidence map›Paper›PMID 26542680›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Direct force measurements reveal that protein Tau confers short-range attractions and isoform-dependent steric stabilization to microtubules.

Peter J Chung, Myung Chul Choi, Herbert P Miller, H Eric Feinstein, Uri Raviv, Youli Li, Leslie Wilson, Stuart C Feinstein, Cyrus R Safinya

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.9field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
  2. Article
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  7. Tau, microtubule dynamics, and axonal transport: New paradigms for neurodegenerative disease.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023
    Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. It's all about tau.Progress in neurobiology · 2019
    Review
  13. Review
  14. Journal of applied crystallography · 2019
    Article
  15. Article
  16. Physical Biology of Axonal Damage.Frontiers in cellular neuroscience · 2018
    Article
  17. Article
  18. Article
  19. Article
  20. A functional role for intrinsic disorder in the tau-tubulin complex.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 3 countries.

Peter J ChungMaterials Department, University of California, Santa Barbara, CA 93106; Physics Department, University of California, Santa Barbara, CA 93106; Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, CA 93106;
Myung Chul ChoiDepartment of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea;
Herbert P MillerMolecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, CA 93106; Neuroscience Research Institute, University of California, Santa Barbara, CA 93106;
H Eric FeinsteinMolecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, CA 93106; Neuroscience Research Institute, University of California, Santa Barbara, CA 93106;
Uri RavivInstitute of Chemistry, Hebrew University of Jerusalem, Jerusalem 91904, Israel;
Youli LiMaterials Research Laboratory, University of California, Santa Barbara, CA 93106.
Leslie WilsonMolecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, CA 93106; Neuroscience Research Institute, University of California, Santa Barbara, CA 93106;
Stuart C FeinsteinMolecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, CA 93106; Neuroscience Research Institute, University of California, Santa Barbara, CA 93106;
Cyrus R SafinyaMaterials Department, University of California, Santa Barbara, CA 93106; Physics Department, University of California, Santa Barbara, CA 93106; Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, CA 93106; safinya@mrl.ucsb.edu.
University of California, Santa Barbara · USHebrew University of Jerusalem · ILKorea Institute of Brain Science · KR

Funding

Mechanism &Control of Brain Microtubule DynamicsR01NS013560 · NINDS · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI WILSON, LESLIE · 1985 to 2009
$2.9M
The Molecular Structure and Function of Tau ProteinR01NS035010 · NINDS · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI FEINSTEIN, STUART C · 1996 to 2010
$2.7M
NINDS NIH HHS R01 NS013560NINDS NIH HHS R01 NS035010NINDS NIH HHS R01-NS13560NINDS NIH HHS R01-NS35010
6 · The paper itself

Abstract

Microtubules (MTs) are hollow cytoskeletal filaments assembled from αβ-tubulin heterodimers. Tau, an unstructured protein found in neuronal axons, binds to MTs and regulates their dynamics. Aberrant Tau behavior is associated with neurodegenerative dementias, including Alzheimer's. Here, we report on a direct force measurement between paclitaxel-stabilized MTs coated with distinct Tau isoforms by synchrotron small-angle X-ray scattering (SAXS) of MT-Tau mixtures under osmotic pressure (P). In going from bare MTs to MTs with Tau coverage near the physiological submonolayer regime (Tau/tubulin-dimer molar ratio; ΦTau = 1/10), isoforms with longer N-terminal tails (NTTs) sterically stabilized MTs, preventing bundling up to PB ∼ 10,000-20,000 Pa, an order of magnitude larger than bare MTs. Tau with short NTTs showed little additional effect in suppressing the bundling pressure (PB ∼ 1,000-2,000 Pa) over the same range. Remarkably, the abrupt increase in PB observed for longer isoforms suggests a mushroom to brush transition occurring at 1/13 < ΦTau < 1/10, which corresponds to MT-bound Tau with NTTs that are considerably more extended than SAXS data for Tau in solution indicate. Modeling of Tau-mediated MT-MT interactions supports the hypothesis that longer NTTs transition to a polyelectrolyte brush at higher coverages. Higher pressures resulted in isoform-independent irreversible bundling because the polyampholytic nature of Tau leads to short-range attractions. These findings suggest an isoform-dependent biological role for regulation by Tau, with longer isoforms conferring MT steric stabilization against aggregation either with other biomacromolecules or into tight bundles, preventing loss of function in the crowded axon environment.

Indexed as

Biophysical PhenomenaAnimalsCattleHumansMicrotubulesModels, MolecularOsmotic PressureProtein BindingProtein Isoformstau ProteinsProtein Isoformstau Proteinsforce measurementintrinsically disordered proteinsmicrotubuleSAXSTau

Identifiers

PMID26542680
PMCPMC4664379
OpenAlexW2142635402

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.