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Synergy between XMAP215 and EB1 increases microtubule growth rates to physiological levels

Nature Cell Biology volume 15, pages 688–693 (2013)Cite this article

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Abstract

In cells, a complex network of proteins regulates the dynamic growth of microtubules that is essential for division and migration. In vitro approaches with purified components have so far been unable to reconstitute fast microtubule growth observed in vivo 1,2,3. Here we show that two well-studied plus-end-binding proteins—end-tracking protein EB1 and microtubule polymerase XMAP215—act together to strongly promote microtubule growth to cellular rates. Unexpectedly, the combined effects of XMAP215 and EB1 are highly synergistic, with acceleration of growth well beyond the product of the individual effects of either protein. The synergistic growth promotion does not rely on any of the canonical EB1 interactions, suggesting an allosteric interaction through the microtubule end. This hypothesis is supported by the finding that taxol and XMAP215, which have non-overlapping binding sites on tubulin, also act synergistically on growth. The increase in growth rates is accompanied by a strong enhancement of microtubule catastrophe by EB1, thereby rendering the fast and dynamic microtubule behaviour typically observed in cells2,4,5,6.

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Figure 1: EB1 and XMAP215 synergistically regulate microtubule dynamics.
Figure 2: Synergy is not a consequence of a direct interaction between EB1 and XMAP215.
Figure 3: Synergistic promotion of growth can also be achieved by XMAP215 in combination with taxol.
Figure 4: Model for catalysis of microtubule growth.

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Acknowledgements

We thank M. Braun (MPI-CBG, Dresden, Germany) for the gift of EB1ΔC protein; S. Reber for help with protein expression and purification; M. Aliee, A. Clarke and M. Neetz, with whom this project was initiated as a part of the PhD programme course; G. Brouhard, S. Diez and M. Gardner for critical evaluation of the manuscript; and members of the Howard laboratory for discussions, reading and feedback. M.Z. was supported by a Cross-Disciplinary Fellowship from the International Human Frontier Science Program Organization. P.O.W. was supported by a European Molecular Biology Organization long-term fellowship.

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  1. Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, 01307 Dresden, Germany

    Marija Zanic, Per O. Widlund, Anthony A. Hyman & Jonathon Howard

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  1. Marija Zanic
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  2. Per O. Widlund
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Contributions

M.Z., P.O.W., A.A.H. and J.H. designed research; M.Z. and P.O.W. performed research; M.Z. and J.H. analysed data; M.Z. and J.H. developed the theoretical model; M.Z., A.A.H. and J.H. wrote the paper.

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Correspondence to Jonathon Howard.

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Zanic, M., Widlund, P., Hyman, A. et al. Synergy between XMAP215 and EB1 increases microtubule growth rates to physiological levels. Nat Cell Biol 15, 688–693 (2013). https://doi.org/10.1038/ncb2744

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