Letter | Published:

Assembly dynamics of microtubules at molecular resolution

Naturevolume 442pages709712 (2006) | Download Citation

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Abstract

Microtubules are highly dynamic protein polymers1 that form a crucial part of the cytoskeleton in all eukaryotic cells. Although microtubules are known to self-assemble from tubulin dimers, information on the assembly dynamics of microtubules has been limited, both in vitro2,3 and in vivo4,5, to measurements of average growth and shrinkage rates over several thousands of tubulin subunits. As a result there is a lack of information on the sequence of molecular events that leads to the growth and shrinkage of microtubule ends. Here we use optical tweezers to observe the assembly dynamics of individual microtubules at molecular resolution. We find that microtubules can increase their overall length almost instantaneously by amounts exceeding the size of individual dimers (8 nm). When the microtubule-associated protein XMAP215 (ref. 6) is added, this effect is markedly enhanced and fast increases in length of about 40–60 nm are observed. These observations suggest that small tubulin oligomers are able to add directly to growing microtubules and that XMAP215 speeds up microtubule growth by facilitating the addition of long oligomers. The achievement of molecular resolution on the microtubule assembly process opens the way to direct studies of the molecular mechanism by which the many recently discovered microtubule end-binding proteins regulate microtubule dynamics in living cells7,8,9.

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Acknowledgements

We thank T. Hyman and T. Mitchison for discussions; K. Kinoshita for help with the purification of XMAP215; S. Tans, K. Kuipers and D. Drechsel for a critical reading of the manuscript; and M. Footer for the gift of axonemes. This work is part of the research program of the Stichting voor Fundamenteel Onderzoek der Materie (FOM), which is supported financially by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO).

Author information

Affiliations

  1. Foundation for Fundamental Research on Matter (FOM) Institute for Atomic and Molecular Physics (AMOLF), Kruislaan 407, 1098 SJ, Amsterdam, The Netherlands

    • Jacob W. J. Kerssemakers
    • , E. Laura Munteanu
    • , Liedewij Laan
    • , Marcel E. Janson
    •  & Marileen Dogterom
  2. Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) Dresden, Pfotenhauerstrasse 108, 01307, Dresden, Germany

    • Jacob W. J. Kerssemakers
    •  & Tim L. Noetzel
  3. Department of Cell and Developmental Biology, University of Pennsylvania, 421 Curie Boulevard, Pennsylvania, 19104-6058, Philadelphia, USA

    • Marcel E. Janson

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Competing interests

Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Corresponding author

Correspondence to Marileen Dogterom.

Supplementary information

  1. Supplementary Methods 1

    Additional methods used in this work. (PDF 24 kb)

  2. Supplementary Methods 2

    Key-hole trap for MT length measurements. The file also contains Supplementary Figure A1 and one reference. (PDF 112 kb)

  3. Supplementary Methods 3

    Step fitting algorithm. The file also contains Supplementary Figures C1–C3. (PDF 184 kb)

  4. Supplementary Data

    Dynamics of freely growing microtubules: effect of XMAP215. The file also contains Supplementary Figure B1, Supplementary Table 1 and one reference. (PDF 42 kb)

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https://doi.org/10.1038/nature04928

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