MAP4 and CLASP1 operate as a safety mechanism to maintain a stable spindle position in mitosis
Abstract
Correct positioning of the mitotic spindle is critical to establish the correct cell-division plane. Spindle positioning involves capture of astral microtubules and generation of pushing/pulling forces at the cell cortex. Here we show that the tau-related protein MAP4 and the microtubule rescue factor CLASP1 are essential for maintaining spindle position and the correct cell-division axis in human cells. We propose that CLASP1 is required to correctly capture astral microtubules, whereas MAP4 prevents engagement of excess dynein motors, thereby protecting the system from force imbalance. Consistent with this, MAP4 physically interacts with dynein-dynactin in vivo and inhibits dynein-mediated microtubule sliding in vitro. Depletion of MAP4, but not CLASP1, causes spindle misorientation in the vertical plane, demonstrating that force generators are under spatial control. These findings have wide biological importance, because spindle positioning is essential during embryogenesis and stem-cell homeostasis.
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The modest effect of MAP4 on the DDH landing rate may be consistent with prior results suggesting MAP4 could inhibit dynein-based movements.
“The modest effect of MAP4 on the DDH landing rate may be consistent with prior results18,19, which suggested MAP4 could inhibit dynein-based movements.”
From Microtubule lattice spacing governs cohesive envelope formation of tau family proteins (2022) · cites this paper as [19]
Cites
Shaner, N. C., Campbell, R. E., Steinbach, P. A., Giepmans, B. N. G., Palmer, A. E., & Tsien, R. Y. (2004) · Nature Biotechnology · doi:10.1038/nbt1037 · Cited by 4,619 · see citing works
Differential Regulation of Dynein and Kinesin Motor Proteins by Tau
Dixit, R., Ross, J. L., Goldman, Y. E., & Holzbaur, E. L. F. (2008) · Science · doi:10.1126/science.1152993 · Cited by 1,012 · see citing works
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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
- Authors
- Samora, C. P., Mogessie, B., Conway, L., Ross, J. L., Straube, A., & McAinsh, A. D.
- Affiliations
- University of Warwick (GB)
- University of Massachusetts Amherst (US)
- Corresponding author
- Straube, Anne
- McAinsh, Andrew D.
- Venue
- Nature Cell Biology
- Published
- 2011-08-07
- Volume
- 13
- Issue
- 9
- Pages
- 1040-1050
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2059025759
- Cited by
- 124
- References
- 2
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 5 · 2023: 5 · 2022: 5 · 2021: 7 · 2020: 7 · 2019: 6 · 2018: 8 · 2017: 12 · 2016: 9 · 2015: 17 · 2014: 11 · 2013: 10 · 2012: 12
- FWCI
- 4.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Explore Bristol Research (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- mitotic spindle positioning, MAP4, CLASP1, astral microtubules, dynein, dynactin, microtubule sliding, microtubule rescue, cell cortex, microtubule-associated proteins, cell division
- MeSH terms
- Dynactin Complex, Cell Division, Cell Line, Cytoskeleton, Dyneins, HeLa Cells, Humans, Luminescent Proteins, Microscopy, Fluorescence, Microtubule-Associated Proteins, Microtubules, Mitosis, Spindle Apparatus, Protein Binding, Immunoblotting, RNA Interference
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