Abstract
An important function of microtubules is to move cellular structures such as chromosomes, mitotic spindles and other organelles around inside cells. This is achieved by attaching the ends of microtubules to cellular structures; as the microtubules grow and shrink, the structures are pushed or pulled around the cell. How do the ends of microtubules couple to cellular structures, and how does this coupling regulate the stability and distribution of the microtubules? It is now clear that there are at least three properties of a microtubule end: it has alternate structures; it has a biochemical transition defined by GTP hydrolysis; and it forms a distinct target for the binding of specific proteins. These different properties can be unified by thinking of the microtubule as a molecular machine, which switches between growing and shrinking modes. Each mode is associated with a specific end structure on which end-binding proteins can assemble to modulate dynamics and couple the dynamic properties of microtubules to the movement of cellular structures.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
196,21 € per year
only 3,85 € per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout





Similar content being viewed by others
References
Doxsey, S. Re-evaluating centrosome function. Nature Rev. Mol. Cell Biol. 2, 688–698 (2001).
Vinh, D. B. N., Kern, J. W., Hancock, W. O., Howard, J. & Davis, T. N. Reconstitution and characterization of budding yeast γ-tubulin complex. Mol. Biol. Cell 13, 1144–1157 (2002).
Meads, T. & Schroer, T. A. Polarity and nucleation of microtubules in polarized epithelial cells. Cell Motil. Cytoskel. 32, 273–288 (1995).
Tassin, A. & Bornens, M. Centrosome structure and microtubule nucleation in animal cells. Biol. Cell 91, 343–354 (1999).
Mitchison, T. & Kirschner, M. Dynamic instability of microtubule growth. Nature 312, 237–242 (1984).
Cassimeris, L., Pryer, N. K. & Salmon, E. D. Real-time observations of microtubule dynamic instability in living cells. J. Cell Biol. 107, 2223–2231 (1988).
Sammak, P. J. & Borisy, G. G. Direct observation of microtubule dynamics in living cells. Nature 332, 724–726 (1988).
Belmont, L. D., Hyman, A. A., Sawin, K. E. & Mitchison, T. J. Real-time visualization of cell cycle-dependent changes in microtubule dynamics in cytoplasmic extracts. Cell 62, 579–589 (1990).
Kinoshita, K., Habermann, B. & Hyman, A. A. XMAP215: a key component of the dynamic microtubule cytoskeleton. Trends Cell Biol. 12, 267–273 (2002).
Kirschner, M. & Mitchison, T. Beyond self-assembly: from microtubules to morphogenesis. Cell 45, 329–342 (1986).
Karsenti, E. Mitotic spindle morphogenesis in animal cells. Semin. Cell Biol. 2, 251–260 (1991).
Hyman, A. A. & Karsenti, E. Morphogenetic properties of microtubules and mitotic spindle assembly. Cell 84, 401–410 (1996).
Hayden, J. H., Bowser, S. S. & Rieder, C. L. Kinetochores capture astral microtubules during chromosome attachment to the mitotic spindle: direct visualization in live newt lung cells. J. Cell Biol. 111, 1039–1045 (1990).
Karsenti, E. & Vernos, I. The mitotic spindle: a self-made machine. Science 294, 543–547 (2001).
Hirokawa, N. Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science 279, 519–526 (1998).
Howard, J. Mechanics of Motor Proteins and the Cytoskeleton (Sinauer Associates, Sunderland, MA, 2001).
Vale, R. D. & Milligan, R. A. The way things move: looking under the hood of molecular motor proteins. Science 288, 88–95 (2000).
Rieder, C. L. & Salmon, E. D. The vertebrate cell kinetochore and its roles during mitosis. Trends Cell Biol. 8, 310–318 (1998).
Inoue, S. & Salmon, E. D. Force generation by microtubule assembly/disassembly in mitosis and related movements. Mol. Biol. Cell 6, 1619–1640 (1995).
Doe, C. Q. & Bowerman, B. Asymmetric cell division: fly neuroblast meets worm zygote. Curr. Opin. Cell Biol. 13, 68–75 (2001).
Gonczy, P. Mechanisms of spindle positioning: focus on flies and worms. Trends Cell Biol. 12, 332–339 (2002).
Tran, P. T., Marsh, L., Doye, V., Inoue, S. & Chang, F. A mechanism for nuclear positioning in fission yeast based on microtubule pushing. J. Cell Biol. 153, 397–412 (2001).
Kusch, J., Meyer, A., Snyder, M. P. & Barral, Y. Microtubule capture by the cleavage apparatus is required for proper spindle positioning in yeast. Genes Dev. 16, 1627–1639 (2002).
Yeh, E. et al. Dynamic positioning of mitotic spindles in yeast: role of microtubule motors and cortical determinants. Mol. Biol. Cell 11, 3949–3961 (2000).
Liakopoulos, D., Kusch, J., Grava, S., Vogel, J. & Barral, Y. Asymmetric loading of Kar9 onto spindle poles and microtubules ensures proper spindle alignment. Cell 112, 561–574 (2003).
Maekawa, H., Usui, T., Knop, M. & Schiebel, E. Yeast Cdk1 translocates to the plus end of cytoplasmic microtubules to regulate bud cortex interactions. EMBO J. 22, 438–449 (2003).
Fygenson, D. K., Marko, J. F. & Libchaber, A. Mechanics of microtubule-based membrane extension. Phys. Rev. Lett. 79, 4497–4500 (1997).
Dogterom, M. & Yurke, B. Measurement of the force-velocity relation for growing microtubules. Science 278, 856–860 (1997).
Coue, M., Lombillo, V. A. & McIntosh, J. R. Microtubule depolymerization promotes particle and chromosome movement in vitro. J. Cell Biol. 112, 1165–1175 (1991).
Faivre-Moskalenko, C. & Dogterom, M. Dynamics of microtubule asters in microfabricated chambers: the role of catastrophes. Proc. Natl Acad. Sci. USA 99, 16788–16793 (2002).
Holy, T. E., Dogterom, M., Yurke, B. & Leibler, S. Assembly and positioning of microtubule asters in microfabricated chambers. Proc. Natl Acad. Sci. USA 94, 6228–6231 (1997).
Erickson, H. P. & O'Brien, E. T. Microtubule dynamic instability and GTP hydrolysis. Annu. Rev. Biophys. Biomol. Struct. 21, 145–166 (1992).
Hyman, A. A., Salser, S., Drechsel, D. N., Unwin, N. & Mitchison, T. J. Role of GTP hydrolysis in microtubule dynamics: information from a slowly hydrolyzable analogue, GMPCPP. Mol. Biol. Cell 3, 1155–1167 (1992).
Desai, A. & Mitchison, T. J. Microtubule polymerization dynamics. Annu. Rev. Cell Dev. Biol. 13, 83–117 (1997).
Mitchison, T. J. Localization of an exchangeable GTP binding site at the plus end of microtubules. Science 261, 1044–1047 (1993).
Nogales, E., Whittaker, M., Milligan, R. A. & Downing, K. H. High-resolution model of the microtubule. Cell 96, 79–88 (1999).
Drechsel, D. N. & Kirschner, M. W. The minimum GTP cap required to stabilize microtubules. Curr. Biol. 4, 1053–1061 (1994). [Published erratum appears in Curr. Biol. 5, 215 (1995).]
Caplow, M. & Shanks, J. Evidence that a single monolayer tubulin-GTP cap is both necessary and sufficient to stabilize microtubules. Mol. Biol. Cell 7, 663–675 (1996).
Geeves, M. A. & Holmes, K. C. Structural mechanism of muscle contraction. Annu. Rev. Biochem. 68, 687–728 (1999).
Chretien, D., Fuller, S. D. & Karsenti, E. Structure of growing microtubule ends: two-dimensional sheets close into tubes at variable rates. J. Cell Biol. 129, 1311–1328 (1995).
Arnal, I., Karsenti, E. & Hyman, A. A. Structural transitions at microtubule ends correlate with their dynamic properties in Xenopus egg extracts. J. Cell Biol. 149, 767–774 (2000).
Mandelkow, E. M., Mandelkow, E. & Milligan, R. A. Microtubule dynamics and microtubule caps: a time-resolved cryo-electron microscopy study. J. Cell Biol. 114, 977–991 (1991).
Melki, R., Carlier, M. F., Pantaloni, D. & Timasheff, S. N. Cold depolymerization of microtubules to double rings: geometric stabilization of assemblies. Biochemistry 28, 9143–9152 (1989).
Hyman, A. A., Chretien, D., Arnal, I. & Wade, R. H. Structural changes accompanying GTP hydrolysis in microtubules: information from a slowly hydrolyzable analogue guanylyl-(α,β)-methylene-diphosphonate. J. Cell Biol. 128, 117–125 (1995).
Muller-Reichert, T., Chretien, D., Severin, F. & Hyman, A. A. Structural changes at microtubule ends accompanying GTP hydrolysis: information from a slowly hydrolyzable analogue of GTP, guanylyl (α,β)methylenediphosphonate. Proc. Natl Acad. Sci. USA 95, 3661–3666 (1998).
Gigant, B. et al. The 4 Å X-ray structure of a tubulin:stathmin-like domain complex. Cell 102, 809–816 (2000).
Andersen, S. S. Spindle assembly and the art of regulating microtubule dynamics by MAPs and Stathmin/Op18. Trends Cell Biol. 10, 261–267 (2000).
Schuyler, S. C. & Pellman, D. Microtubule “plus-end-tracking proteins”: The end is just the beginning. Cell 105, 421–424 (2001).
Mimori-Kiyosue, Y. & Tsukita, S. Where is APC going? J. Cell Biol. 154, 1105–1109 (2001).
Tirnauer, J. S. & Bierer, B. E. EB1 proteins regulate microtubule dynamics, cell polarity, and chromosome stability. J. Cell Biol. 149, 761–766 (2000).
Kim, A. J. & Endow, S. A. A kinesin family tree. J. Cell Sci. 113, 3681–3682 (2000).
Lawrence, C. J., Malmberg, R. L., Muszynski, M. G. & Dawe, R. K. Maximum likelihood methods reveal conservation of function among closely related kinesin families. J. Mol. Evol. 54, 42–53 (2002).
Desai, A., Verma, S., Mitchison, T. J. & Walczak, C. E. Kin I kinesins are microtubule-destabilizing enzymes. Cell 96, 69–78 (1999).
Hunter, A. W. et al. The kinesin-related protein MCAK is a microtubule depolymerase that forms an ATP-hydrolyzing complex at microtubule ends. Mol. Cell (in the press).
Walczak, C. E., Mitchison, T. J. & Desai, A. XKCM1: a Xenopus kinesin-related protein that regulates microtubule dynamics during mitotic spindle assembly. Cell 84, 37–47 (1996).
Tournebize, R. et al. Control of microtubule dynamics by the antagonistic activities of XMAP215 and XKCM1 in Xenopus egg extracts. Nature Cell Biol. 2, 13–19 (2000).
Maney, T., Wagenbach, M. & Wordeman, L. Molecular dissection of the microtubule depolymerizing activity of mitotic centromere-associated kinesin. J. Biol. Chem. 276, 34753–34758 (2001).
Maney, T., Hunter, A. W., Wagenbach, M. & Wordeman, L. Mitotic centromere-associated kinesin is important for anaphase chromosome segregation. J. Cell Biol. 142, 787–801 (1998).
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).
Moores, C. A. et al. A mechanism for microtubule depolymerization by KinI kinesins. Mol. Cell 9, 903–909 (2002).
Niederstrasser, H., Salehi-Had, H., Gan, E. C., Walczak, C. & Nogales, E. XKCM1 acts on a single protofilament and requires the C terminus of tubulin. J. Mol. Biol. 316, 817–828 (2002).
Janosi, I. M., Chretien, D. & Flyvbjerg, H. Structural microtubule cap: stability, catastrophe, rescue, and third state. Biophys. J. 83, 1317–1330 (2002).
Perez, F., Diamantopoulos, G. S., Stalder, R. & Kreis, T. E. CLIP-170 highlights growing microtubule ends in vivo. Cell 96, 517–527 (1999).
Komarova, Y. A., Akhmanova, A. S., Kojima, S.-i., Galjart, N. & Borisy, G. G. Cytoplasmic linker proteins promote microtubule rescue in vivo. J. Cell Biol. 159, 589–599 (2002).
Brunner, D. & Nurse, P. CLIP170-like tip1p spatially organizes microtubular dynamics in fission yeast. Cell 102, 695–704 (2000).
Lin, H. et al. Polyploids require Bik1 for kinetochore-microtubule attachment. J. Cell Biol. 155, 1173–1184 (2001).
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).
Small, J. V. & Kaverina, I. Microtubules meet substrate adhesions to arrange cell polarity. Curr. Opin. Cell Biol. 15, 40–47 (2003).
Sawin, K. E. Microtubule dynamics: the view from the tip. Curr. Biol. 10, R860–R862 (2000).
Schroer, T. A. Microtubules don and doff their caps: dynamic attachments at plus and minus ends. Curr. Opin. Cell Biol. 13, 92–96 (2001).
Akhmanova, A. et al. Clasps are CLIP-115 and -170 associating proteins involved in the regional regulation of microtubule dynamics in motile fibroblasts. Cell 104, 923–935 (2001).
Tirnauer, J. S., Grego, S., Salmon, E. D. & Mitchison, T. J. EB1-microtubule interactions in Xenopus egg extracts: role of EB1 in microtubule stabilization and mechanisms of targeting to microtubules. Mol. Biol. Cell 13, 3614–3626 (2002).
He, X., Rines, D. R., Espelin, C. W. & Sorger, P. K. Molecular analysis of kinetochore-microtubule attachment in budding yeast. Cell 106, 195–206 (2001).
Lee, L. et al. Positioning of the mitotic spindle by a cortical-microtubule capture mechanism. Science 287, 2260–2262 (2000).
Maekawa, H., Usui, T., Knop, M. & Schiebel, E. Yeast Cdk1 translocates to the plus end of cytoplasmic microtubules to regulate bud cortex interactions. EMBO J. 22, 438–449 (2003).
Hildebrandt, E. R. & Hoyt, M. A. Mitotic motors in Saccharomyces cerevisiae. Biochim. Biophys. Acta 1496, 99–116 (2000).
Valetti, C. et al. Role of dynactin in endocytic traffic: effects of dynamitin overexpression and colocalization with CLIP-170. Mol. Biol. Cell 10, 4107–4120 (1999).
Loisel, T. P., Boujemaa, R., Pantaloni, D. & Carlier, M. F. Reconstitution of actin-based motility of Listeria and Shigella using pure proteins. Nature 401, 613–616 (1999).
Acknowledgements
We thank Y. Barral and G. Borisy for sharing unpublished data. Research in the authors' laboratories is supported by the Human Frontier Science Program, the National Institutes of Health and the Max Planck Gesellschaft.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Howard, J., Hyman, A. Dynamics and mechanics of the microtubule plus end. Nature 422, 753–758 (2003). https://doi.org/10.1038/nature01600
Issue Date:
DOI: https://doi.org/10.1038/nature01600