Doublecortin Is Excluded from Growing Microtubule Ends and Recognizes the GDP-Microtubule Lattice
Open accessAbstract
Many microtubule (MT) functions are mediated by a diverse class of proteins (+TIPs) at growing MT plus ends that control intracellular MT interactions and dynamics and depend on end-binding proteins (EBs) [1]. Cryoelectron microscopy has recently identified the EB binding site as the interface of four tubulin dimers that undergoes a conformational change in response to β-tubulin GTP hydrolysis [2, 3]. Doublecortin (DCX), a MT-associated protein (MAP) required for neuronal migration during cortical development [4, 5], binds to the same site as EBs [6], and recent in vitro studies proposed DCX localization to growing MT ends independent of EBs [7]. Because this conflicts with observations in neurons [8, 9] and the molecular function of DCX is not well understood, we revisited intracellular DCX dynamics at low expression levels. Here, we report that DCX is not a +TIP in cells but, on the contrary, is excluded from the EB1 domain. In addition, we find that DCX-MT interactions are highly sensitive to MT geometry. In cells, DCX binding was greatly reduced at MT segments with high local curvature. Remarkably, this geometry-dependent binding to MTs was completely reversed in the presence of taxanes, which reconciles incompatible observations in cells [9] and in vitro [10]. We propose a model explaining DCX specificity for different MT geometries based on structural changes induced by GTP hydrolysis that decreases the spacing between adjacent tubulin dimers [11]. Our data are consistent with a unique mode of MT interaction in which DCX specifically recognizes this compacted GDP-like MT lattice.
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After adding 0.01 μM taxol to U-2 OS cells, tau dissociated from microtubules in all cells, as quantified by a decrease in the coefficient of variation of the tau signal.
“We added 0.01 μM taxol to the medium and imaged the cells for 10 minutes while monitoring the tau density on microtubules initially fully covered by eGFP-tau. In line with our in vitro observations, and previous in vivo evidence33,35, we observed that in all cells tau dissociated from the microtubules (Fig. 4a, Supplementary Movie 9) as quantified by the decrease in the coefficient of variation of”
From Microtubule lattice spacing governs cohesive envelope formation of tau family proteins (2022) · cites this paper as [35]
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Research works printed but not linked: 28
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Microtubule lattice spacing governs cohesive envelope formation of tau family proteins
Siahaan, V., Tan, R., Humhalova, T., Libusova, L., Lacey, S. E., Tan, T., Dacy, M., Ori-McKenney, K. M., McKenney, R. J., Braun, M., et al. (2022) · Nature Chemical Biology · doi:10.1038/s41589-022-01096-2 · Cited by 94 · see citing works
StableMARK-decorated microtubules in cells have expanded lattices
de Jager, L., Jansen, K. I., Hoogebeen, R., Akhmanova, A., Kapitein, L. C., Förster, F., & Howes, S. C. (2025) · Journal of Cell Biology · doi:10.1083/jcb.202206143 · Cited by 25 · see citing works
- Authors
- Ettinger, A., van Haren, J., Ribeiro, S. A., & Wittmann, T.
- Affiliations
- University of California, San Francisco (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Wittmann, Torsten
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 26
- Issue
- 12
- Pages
- 1549-1555
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC5023073
- OpenAlex
- W2395604477
- Cited by
- 55
- References
- 0
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 8 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 7 · 2017: 6 · 2016: 1
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Site cant be reached (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of General Medical Sciences (R01GM079139)
- National Center for Research Resources (S10RR026758)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- doublecortin, microtubule plus ends, end-binding proteins, EB1, GTP hydrolysis, paclitaxel, neuronal migration, microtubule-associated proteins
- MeSH terms
- Doublecortin Domain Proteins, Doublecortin Protein, Guanosine Diphosphate, Humans, Microtubule-Associated Proteins, Microtubules, Neuropeptides, Cell Line, Tumor
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