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Assembly dynamics of microtubules at molecular resolution

Naturevolume 442pages709712 (2006) | Download Citation



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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  1. 1

    Desai, A. & Mitchison, T. J. Microtubule polymerization dynamics. Annu. Rev. Cell Dev. Biol. 13, 83–117 (1997)

  2. 2

    Walker, R. A. et al. Dynamic instability of individual microtubules analyzed by video light-microscopy—rate constants and transition frequencies. J. Cell Biol. 107, 1437–1448 (1988)

  3. 3

    Fygenson, D. K., Braun, E. & Libchaber, A. Phase diagram of microtubules. Phys. Rev. E 50, 1579–1588 (1994)

  4. 4

    Komarova, Y. A., Vorobjev, I. A. & Borisy, G. G. Life cycle of MTs: persistent growth in the cell interior, asymmetric transition frequencies and effects of the cell boundary. J. Cell Sci. 115, 3527–3539 (2002)

  5. 5

    Piehl, M. & Cassimeris, L. Organization and dynamics of growing microtubule plus ends during early mitosis. Mol. Biol. Cell 14, 916–925 (2003)

  6. 6

    Kinoshita, K., Habermann, B. & Hyman, A. A. XMAP215: a key component of the dynamic microtubule cytoskeleton. Trends Cell Biol. 12, 267–273 (2002)

  7. 7

    Schuyler, S. C. & Pellman, D. Microtubule ‘plus-end-tracking proteins’: the end is just the beginning. Cell 105, 421–424 (2001)

  8. 8

    Howard, J. & Hyman, A. A. Dynamics and mechanics of the microtubule plus end. Nature 422, 753–758 (2003)

  9. 9

    Akhmanova, A. & Hoogenraad, C. C. Microtubule plus-end-tracking proteins: mechanisms and functions. Curr. Opin. Cell Biol. 17, 47–54 (2005)

  10. 10

    Chretien, D., Fuller, S. D. & Karsenti, E. Structure of growing microtubule ends—2-dimensional sheets close into tubes at variable rates. J. Cell Biol. 129, 1311–1328 (1995)

  11. 11

    Wang, H.-W. & Nogales, E. Nucleotide-dependent bending flexibility of tubulin regulates microtubule assembly. Nature 435, 911–915 (2005)

  12. 12

    Wang, H.-W., Long, S., Finley, K. R. & Nogales, E. Assembly of GMPCPP-bound tubulin into helical ribbons and tubes and effect of colchicine. Cell Cycle 4, 1157–1160 (2005)

  13. 13

    Kerssemakers, J. W. J., Janson, M. E., Van der Horst, A. & Dogterom, M. Optical trap setup for measuring microtubule pushing forces. Appl. Phys. Lett. 83, 4441–4443 (2003)

  14. 14

    Gard, D., Becker, B. & Romney, S. MAPping the eukaryotic tree of life: Structure, function, and evolution of the MAP215/Dis1 family of microtubule-associated proteins. Int. Rev. Cytol. 239, 179–272 (2004)

  15. 15

    Gard, D. L. & Kirschner, M. W. A microtubule-associated protein from Xenopus eggs that specifically promotes assembly at the plus-end. J. Cell Biol. 105, 2203–2215 (1987)

  16. 16

    Vasquez, R. J., Gard, D. L. & Lynne, C. XMAP from Xenopus eggs promotes rapid plus end assembly of microtubules and rapid microtubule polymer turnover. J. Cell Biol. 127, 985–993 (1994)

  17. 17

    Kinoshita, K., Arnal, I., Desai, A., Drechsel, D. N. & Hyman, A. A. Reconstitution of physiological microtubule dynamics using purified components. Science 294, 1340–1343 (2001)

  18. 18

    Dogterom, M. & Yurke, B. Measurement of the force-velocity relation for growing microtubules. Science 278, 856–860 (1997)

  19. 19

    Janson, M. E., de Dood, M. E. & Dogterom, M. Dynamic instability of microtubules is regulated by force. J. Cell Biol. 161, 1029–1034 (2003)

  20. 20

    Janson, M. E. & Dogterom, M. Scaling of microtubule force–velocity curves obtained at different tubulin concentrations. Phys. Rev. Lett. 92, 248101 (2004)

  21. 21

    Shirasu-Hiza, M., Coughlin, P. & Mitchison, T. Identification of XMAP215 as a microtubule-destabilizing factor in Xenopus egg extract by biochemical purification. J. Cell Biol. 161, 349–358 (2003)

  22. 22

    Cassimeris, L., Gard, D., Tran, P. T. & Erickson, H. P. XMAP215 is a long thin molecule that does not increase microtubule stiffness. J. Cell Sci. 114, 3025–3033 (2001)

  23. 23

    Janosi, I. M., Chretien, D. & Flyvberg, H. Modeling elastic properties of microtubule tips and walls. Eur. Biophys. J. 27, 501–513 (1998)

  24. 24

    Spittle, C., Charrasse, S., Larroque, C. & Cassimeris, L. The interaction of TOGp with microtubules and tubulin. J. Biol. Chem. 275, 20748–20753 (2000)

  25. 25

    VanBuren, V., Cassimeris, L. & Odde, D. J. A mechanochemical model of microtubule structure and self-assembly kinetics. Biophys. J. 89, 2911–2926 (2005)

  26. 26

    Diamantopoulos, G. S. et al. Dynamic localization of CLIP-170 to microtubule plus ends is coupled to microtubule assembly. J. Cell Biol. 144, 99–112 (1999)

  27. 27

    Arnal, I., Heichette, C., Diamantopoulos, G. S. & Chretien, D. CLIP-170/tubulin-curved oligomers coassemble at microtubule ends and promote rescues. Curr. Biol. 14, 2086–2095 (2004)

  28. 28

    Folker, E. S., Baker, B. M. & Goodson, H. V. Interactions between CLIP-170, tubulin, and microtubules: implications for the mechanism of CLIP-170 plus-end tracking behaviour. Mol. Biol. Cell 16, 5373–5384 (2005)

  29. 29

    Schek, H. T. III & Hunt, A. J. Micropatterned structures for studying the mechanics of biological polymers. Biomed. Microdevices 7, 41–46 (2005)

  30. 30

    Pierce, D. W. & Vale, R. D. Assaying processive movement of kinesin by fluorescence microscopy. Methods. Enzymol. 298, 154–171 (1998)

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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


  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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