Mammalian end binding proteins control persistent microtubule growth
Open accessAbstract
End binding proteins (EBs) are highly conserved core components of microtubule plus-end tracking protein networks. Here we investigated the roles of the three mammalian EBs in controlling microtubule dynamics and analyzed the domains involved. Protein depletion and rescue experiments showed that EB1 and EB3, but not EB2, promote persistent microtubule growth by suppressing catastrophes. Furthermore, we demonstrated in vitro and in cells that the EB plus-end tracking behavior depends on the calponin homology domain but does not require dimer formation. In contrast, dimerization is necessary for the EB anti-catastrophe activity in cells; this explains why the EB1 dimerization domain, which disrupts native EB dimers, exhibits a dominant-negative effect. When microtubule dynamics is reconstituted with purified tubulin, EBs promote rather than inhibit catastrophes, suggesting that in cells EBs prevent catastrophes by counteracting other microtubule regulators. This probably occurs through their action on microtubule ends, because catastrophe suppression does not require the EB domains needed for binding to known EB partners.
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mCherry-EB3 alone increases the microtubule growth rate as well as the catastrophe and rescue frequencies.
“mCherry-EB3 alone increased the MT growth rate as well as the catastrophe and rescue frequencies, similar to what we observed previously [13]”
From In vitro reconstitution of the functional interplay between MCAK and EB3 at microtubule plus ends (2010) · cites this paper as [13]
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In vitro reconstitution of the functional interplay between MCAK and EB3 at microtubule plus ends
Montenegro Gouveia, S., Leslie, K., Kapitein, L. C., Buey, R. M., Grigoriev, I., Wagenbach, M., Smal, I., Meijering, E., Hoogenraad, C. C., Wordeman, L., et al. (2010) · Current Biology · doi:10.1016/j.cub.2010.08.020 · Cited by 147 · see citing works
Self-citationLaFrance, B. J., Roostalu, J., Henkin, G., Greber, B. J., Zhang, R., Normanno, D., McCollum, C. O., Surrey, T., & Nogales, E. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2114994119 · Cited by 100 · see citing works
- Authors
- Komarova, Y., De Groot, C. O., Grigoriev, I., Gouveia, S. M., Munteanu, E. L., Schober, J. M., Honnappa, S., Buey, R. M., Hoogenraad, C. C., Dogterom, M., Borisy, G. G., Steinmetz, M. O., & Akhmanova, A.
- Affiliations
- Northwestern University (US)
- Biomolecular Research, Structural Biology, Paul Scherrer Insititut, CH-5232 Villigen PSI, Switzerland 2
- Erasmus MC (NL)
- Institute for Atomic and Molecular Physics (NL)
- Paul Scherrer Institute (CH)
- Corresponding author
- Akhmanova, Anna
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2009-03-02
- Volume
- 184
- Issue
- 5
- Pages
- 691-706
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2686402
- OpenAlex
- W2099220194
- Cited by
- 387
- References
- 49
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 14 · 2023: 22 · 2022: 19 · 2021: 20 · 2020: 14 · 2019: 14 · 2018: 17 · 2017: 26 · 2016: 25 · 2015: 30 · 2014: 32 · 2013: 25 · 2012: 35
- FWCI
- 15.87
- 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)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- AMOLF Institutional Repository (AMOLF) (submittedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Open Access Server of the Woods Hole Scientific Community (Woods Hole Scientific Community) (submittedVersion, cc-by-nc-sa)
- Funders
- National Science Foundation
- Ariad Pharmaceuticals
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (109423, 3100A0)
- National Institutes of Health
- University of California, San Diego
- RIKEN
- National Institute of General Medical Sciences (GM 25062, R37GM025062, R01GM025062)
- 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
- end-binding proteins, EB1, EB3, microtubule plus-end tracking, microtubule dynamics, microtubule catastrophe, calponin homology domain, protein dimerization, dominant negative effect
- MeSH terms
- Animals, Cell Differentiation, Cricetulus, Cricetinae, Humans, Microtubule-Associated Proteins, Microtubules, CHO Cells, Protein Structure, Tertiary, Dimerization, Protein Multimerization
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