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Cited by 38Microtubule and mitosis dynamicsCancer Treatment and PharmacologyCellular Mechanics and Interactions

Lattice defects induced by microtubule-stabilizing agents exert a long-range effect on microtubule growth by promoting catastrophes

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Rai, Ankit, Liu, Tianyang, Katrukha, Eugene A., Estévez-Gallego, Juan, Manka, Szymon W., Paterson, Ian, Díaz, J. Fernando, Kapitein, Lukas C. +2 more·2021·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.2112261118PMC PMC8713758

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Abstract

Significance: Microtubules are major cytoskeletal filaments important for cell division, growth, and differentiation. Microtubules can rapidly switch between phases of growth and shortening, and this dynamic behavior is essential for shaping microtubule arrays. To obtain insights into mechanisms controlling microtubule dynamics, here we used microtubule-stabilizing agents such as Taxol and their fluorescent analogs to manipulate microtubule protofilament number and generate stable defects in microtubule lattices that can be visualized using fluorescence microscopy. We show that microtubule polymerization rate increases with protofilament number and that drug-induced microtubule lattice discontinuities can promote plus-end catastrophes at a distance of several micrometers. Our data indicate that structural defects in the microtubule wall can have long-range propagating effects on microtubule tip dynamics.

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Authors
Rai, A., Liu, T., Katrukha, E. A., Estévez-Gallego, J., Manka, S. W., Paterson, I., Díaz, J. F., Kapitein, L. C., Moores, C. A., & Akhmanova, A.
Affiliations
  • Utrecht University (NL)
  • Institute of Structural and Molecular Biology (GB)
  • Structural and Chemical Biology, Centro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas 28040 Madrid, Spain;
  • University of Cambridge (GB)
  • Consejo Superior de Investigaciones Científicas (ES)
Corresponding author
Akhmanova, Anna
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2021-12-16
Volume
118
Issue
51
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.2112261118
PMC
PMC8713758
OpenAlex
W4226164766
Cited by
38
References
67
Citations by year
2026: 6 · 2025: 5 · 2024: 5 · 2023: 13 · 2022: 6 · 2021: 3
FWCI
3.52
Type
journal article
Language
en
Open access
Licence
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • BIROn (Birkbeck, University of London) (acceptedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Chuo University
  • Ministerio de Ciencia, Innovación y Universidades (PID2019, PID2019-104545RB-I00)
  • Eidgenössische Technische Hochschule Zürich
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (711.015.005)
  • Lomonosov Moscow State University
  • Directorate for Biological Sciences
  • Medical Research Council (MR/R000352/1)
  • Biotechnology and Biological Sciences Research Council (BB/N018176/1)
  • Consejo Superior de Investigaciones Científicas
  • FP7 Ideas: European Research Council (609822)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
microtubule catastrophe, microtubule growth, protofilament number, microtubule-stabilizing agents, microtubule dynamics, microtubule severing, microtubule nucleation, cytoskeleton
MeSH terms
Biological Phenomena, Microtubule-Associated Proteins, Microtubules, Protein Binding, Tubulin, Paclitaxel, Tubulin Modulators, Polymerization

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