Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

How do microtubules guide migrating cells?

Nature Reviews Molecular Cell Biology volume 3, pages 957–964 (2002)Cite this article

Abstract

Microtubules have long been implicated in the polarization of migrating cells, but how they carry out this role is unclear. Here, we propose that microtubules determine cell polarity by modulating the pattern of adhesions that a cell develops with the underlying matrix, through focal inhibitions of contractility.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The actin cytoskeleton and adhesion sites in a migrating cell.
Figure 2: Changes in the actin cytoskeleton and adhesion sites in a migrating cell.
Figure 3: Focal adhesion growth in response to the local application of external force.
Figure 4: Microtubule disruption triggers focal adhesion growth.
Figure 5: Microtubules target substrate adhesion complexes.
Figure 6: Asymmetric relaxation of contractility restores polarization in fibroblasts lacking microtubules.
Figure 7: Microtubule–adhesion-site crosstalk in a migrating cell.

Similar content being viewed by others

References

  1. Vasiliev, J. M. et al. Effect of colcemid on the locomotory behaviour of fibroblasts. J. Embryol. Exp. Morphol. 24, 625–640 (1970).

    CAS  PubMed  Google Scholar 

  2. Small, J. V., Stradal, T., Vignal, E. & Rottner, K. The lamellipodium: where motility begins. Trends Cell Biol. 12, 112–120 (2002).

    Article  CAS  PubMed  Google Scholar 

  3. Chen, W. -T. Mechanism of retraction of the trailing edge during fibroblast movement. J. Cell Biol. 90, 187–200 (1981).

    Article  CAS  PubMed  Google Scholar 

  4. Jay, P. Y., Pham, P. A., Wong, S. A. & Elson, E. L. A mechanical function of myosin II in cell motility. J. Cell Sci. 108, 387–393 (1995).

    CAS  PubMed  Google Scholar 

  5. Geiger, B., Bershadsky, A., Pankov, R. & Yamada, K. M. Transmembrane extracellular matrix–cytoskeleton crosstalk. Nature Rev. Mol. Cell Biol. 2, 793–805 (2001).

    Article  CAS  Google Scholar 

  6. Nobes, C. D. & Hall, A. Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81, 53–62 (1995).

    Article  CAS  PubMed  Google Scholar 

  7. Rottner, K., Hall, A. & Small, J. V. Interplay between Rac and Rho in the control of substrate contact dynamics. Curr. Biol. 9, 640–648 (1999).

    Article  CAS  PubMed  Google Scholar 

  8. Smilenov, L. B., Mikhailov, A., Pelham, R. J., Marcantonio, E. E. & Gundersen, G. G. Focal adhesion motility revealed in stationary fibroblasts. Science 286, 1172–1174 (1999).

    Article  CAS  PubMed  Google Scholar 

  9. Zamir, E. et al. Dynamics and segregation of cell–matrix adhesions in cultured fibroblasts. Nature Cell Biol. 2, 191–196 (2000).

    Article  CAS  PubMed  Google Scholar 

  10. Ballestrem, C., Hinz, B., Imhof, B. A. & Wehrle-Haller, B. Marching at the front and dragging behind: differential αVβ3-integrin turnover regulates focal adhesion behavior. J. Cell Biol. 155, 1319–1332 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kaverina, I. et al. Enforced polarisation and locomotion of fibroblasts lacking microtubules. Curr. Biol. 10, 739–742 (2000).

    Article  CAS  PubMed  Google Scholar 

  12. Anderson, K. I. & Cross, R. Contact dynamics during keratocyte motility. Curr. Biol. 10, 253–260 (2000).

    Article  CAS  PubMed  Google Scholar 

  13. Chrzanowska-Wodnicka, M. & Burridge, K. Rho-stimulated contractility drives the formation of stress fibers and focal adhesions. J. Cell Biol. 133, 1403–1415 (1996).

    Article  CAS  PubMed  Google Scholar 

  14. Geiger, B. & Bershadsky, A. Assembly and mechanosensory function of focal contacts. Curr. Opin. Cell Biol. 13, 584–592 (2001).

    Article  CAS  PubMed  Google Scholar 

  15. Ridley, A. J. & Hall, A. The small GTP-binding protein Rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70, 389–399 (1992).

    Article  CAS  PubMed  Google Scholar 

  16. Helfman, D. M. et al. Caldesmon inhibits nonmuscle cell contractility and interferes with the formation of focal adhesions. Mol. Biol. Cell 10, 3097–3112 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Webb, D. J., Parsons, J. T. & Horwitz, A. F. Adhesion assembly, disassembly and turnover in migrating cells — over and over and over again. Nature Cell Biol. 4, E97–E100 (2002).

    Article  CAS  PubMed  Google Scholar 

  18. Riveline, D. et al. Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism. J. Cell Biol. 153, 1175–1186 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kaverina, I. et. al. Tensile stress stimulates microtubule outgrowth in living cells. J. Cell Sci. 115, 2283–2291 (2002).

    CAS  PubMed  Google Scholar 

  20. Watanabe, N., Kato, T., Fujita, A., Ishizaki, T. & Narumiya, S. Cooperation between mDia1 and ROCK in Rho-induced actin reorganization. Nature Cell Biol. 1, 136–143 (1999).

    Article  CAS  PubMed  Google Scholar 

  21. Beningo, K. A., Dembo, M., Kaverina, I., Small, J. V. & Wang, Y. L. Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts. J. Cell Biol. 153, 881–888 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Balaban, N. Q. et al. Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nature Cell Biol. 3, 466–472 (2001).

    Article  CAS  PubMed  Google Scholar 

  23. Beningo, K. A. & Wang, Y. L. Flexible substrata for the detection of cellular traction forces. Trends Cell Biol. 12, 79–84 (2002).

    Article  CAS  PubMed  Google Scholar 

  24. Oliver, T., Dembo, M. & Jacobson, K. Separation of propulsive and adhesive traction stresses in locomoting keratocytes. J. Cell Biol. 145, 589–604 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Bershadsky, A., Chausovsky, A., Becker, E., Lyubimova, A. & Geiger, B. Involvement of microtubules in the control of adhesion-dependent signal transduction. Curr. Biol. 6, 1279–1289 (1996).

    Article  CAS  PubMed  Google Scholar 

  26. Enomoto, T. Microtubule disruption induces the formation of actin stress fibers and focal adhesions in cultured cells: possible involvement of the rho signal cascade. Cell Struct. Funct. 21, 317–326 (1996).

    Article  CAS  PubMed  Google Scholar 

  27. Liu, B. P., Chrzanowska-Wodnicka, M. & Burridge, K. Microtubule depolymerization induces stress fibers, focal adhesions, and DNA synthesis via the GTP-binding protein Rho. Cell Adhes. Commun. 5, 249–255 (1998).

    Article  CAS  PubMed  Google Scholar 

  28. Pletjushkina, O. J. et al. Maturation of cell–substratum focal adhesions induced by depolymerization of microtubules is mediated by increased cortical tension. Cell Adhes. Commun. 5, 121–135 (1998).

    Article  CAS  PubMed  Google Scholar 

  29. Krylyshkina, O. et al. Modulation of substrate adhesion dynamics via microtubule targeting requires kinesin-1. J. Cell Biol. 156, 349–360 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Danowski, B. A. Fibroblast contractility and actin organization are stimulated by microtubule inhibitors. J. Cell Sci. 93, 255–266 (1989).

    CAS  PubMed  Google Scholar 

  31. Kaverina, I., Krylyshkina, O. & Small, J. V. Microtubule targeting of substrate contacts promotes their relaxation and dissociation. J. Cell Biol. 146, 1033–1044 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kaverina, I., Rottner, K. & Small, J. V. Targeting, capture, and stabilization of microtubules at early focal adhesions. J. Cell Biol. 142, 181–190 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ishizaki, T. et al. Coordination of microtubules and the actin cytoskeleton by the Rho effector mDia1. Nature Cell Biol. 3, 8–14 (2001).

    Article  CAS  PubMed  Google Scholar 

  34. Palazzo, A. F., Cook, T. A., Alberts, A. S. & Gundersen, G. G. mDia mediates Rho-regulated formation and orientation of stable microtubules. Nature Cell Biol. 3, 723–729 (2001).

    Article  CAS  PubMed  Google Scholar 

  35. Suter, D. M., Errante, L. D., Belotserkovsky, V. & Forscher, P. The Ig superfamily cell adhesion molecule, apCAM, mediates growth cone steering by substrate–cytoskeletal coupling. J. Cell Biol. 141, 227–240 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Schaefer, A. W., Kabir, N. & Forscher, P. Filopodia and actin arcs guide the assembly and transport of two populations of microtubules with unique dynamic parameters in neuronal growth cones. J. Cell Biol. 158, 139–152 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Salmon, W. C., Adams, M. C. & Waterman-Storer, C. M. Dual-wavelength fluorescent speckle microscopy reveals coupling of microtubule and actin movements in migrating cells. J. Cell Biol. 158, 31–37 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Dunn, G. A. in Cell Adhesion and Motility (eds Curtis, A. S. G. & Pitts, J. D.) 409–423 (Cambridge Univ. Press, Cambridge, UK, 1980).

    Google Scholar 

  39. Dunn, G. A. & Zicha, D. Dynamics of fibroblast spreading. J. Cell Sci. 108, 1239–1249 (1995).

    CAS  PubMed  Google Scholar 

  40. Verkhovsky, A. B., Svitkina, T. M. & Borisy, G. G. Self-polarization and directional motility of cytoplasm. Curr. Biol. 9, 11–20 (1999).

    Article  CAS  PubMed  Google Scholar 

  41. Ballestrem, C., Wehrle-Haller, B., Hinz, B. & Imhof, B. A. Actin-dependent lamellipodia formation and microtubule-dependent tail retraction control-directed cell migration. Mol. Biol. Cell 11, 2999–3012 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kirschner, M. & Mitchison, T. Beyond self-assembly: from microtubules to morphogenesis. Cell 45, 329–342 (1986).

    Article  CAS  PubMed  Google Scholar 

  43. Kaverina, I., Krylyshkina, O. & Small, J. V. Regulation of substrate adhesion dynamics during cell motility. Int. J. Biochem. Cell Biol. 34, 746–761 (2002).

    Article  CAS  PubMed  Google Scholar 

  44. Wittmann, T. & Waterman-Storer, C. M. Cell motility: can Rho GTPases and microtubules point the way? J. Cell Sci. 114, 3795–3803 (2001).

    CAS  PubMed  Google Scholar 

  45. Krendel, M., Zenke, F. T. & Bokoch, G. M. Nucleotide exchange factor GEF-H1 mediates cross-talk between microtubules and the actin cytoskeleton. Nature Cell Biol. 4, 294–301 (2002).

    Article  CAS  PubMed  Google Scholar 

  46. Euteneuer, U. & Schliwa, M. Persistent, directional motility of cells and cytoplasmic fragments in the absence of microtubules. Nature 310, 58–61 (1984).

    Article  CAS  PubMed  Google Scholar 

  47. Keller, H. U., Naef, A. & Zimmermann, A. Effects of colchicine, vinblastine and nocodazole on polarity, motility, chemotaxis and cAMP levels of human polymorphonuclear leukocytes. Exp. Cell Res. 153, 173–185 (1984).

    Article  CAS  PubMed  Google Scholar 

  48. Glasgow, J. E. & Daniele, R. P. Role of microtubules in random cell migration: stabilization of cell polarity. Cell Motil. Cytoskeleton 27, 88–96 (1994).

    Article  CAS  PubMed  Google Scholar 

  49. Sroka, J., von Gunten, M., Dunn, G. A. & Keller, H. U. Phenotype modulation in non-adherent and adherent sublines of Walker carcinosarcoma cells: the role of cell–substratum contacts and microtubules in controlling cell shape, locomotion and cytoskeletal structure. Int. J. Biochem. Cell Biol. 34, 882–899 (2002).

    Article  CAS  PubMed  Google Scholar 

  50. Goode, B. L., Drubin, D. G. & Barnes, G. Functional cooperation between the microtubule and actin cytoskeletons. Curr. Opin. Cell Biol. 12, 63–71 (2000).

    Article  CAS  PubMed  Google Scholar 

  51. Schroer, T. A. Microtubules don and doff their caps: dynamic attachments at plus and minus ends. Curr. Opin. Cell Biol. 13, 92–96 (2001).

    Article  CAS  PubMed  Google Scholar 

  52. Kolodney, M. S. & Wysolmerski, R. B. Isometric contraction by fibroblasts and endothelial cells in tissue culture: a quantitative study. J. Cell Biol. 117, 73–82 (1992).

    Article  CAS  PubMed  Google Scholar 

  53. Brown, R. A., Talas, G., Porter, R. A., McGrouther, D. A. & Eastwood, M. Balanced mechanical forces and microtubule contribution to fibroblast contraction. J. Cell Physiol. 169, 439–447 (1996).

    Article  CAS  PubMed  Google Scholar 

  54. Lyass, L. A., Bershadsky, A. D., Vasiliev, J. M. & Gelfand, I. M. Microtubule-dependent effect of phorbol ester on the contractility of cytoskeleton of cultured fibroblasts. Proc. Natl Acad. Sci. USA 85, 9538–9541 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Solomon, F. & Magendantz, M. Cytochalasin separates microtubule disassembly from loss of asymmetric morphology. J. Cell Biol. 89, 157–161 (1981).

    Article  CAS  PubMed  Google Scholar 

  56. Canman, J. C. & Bement, W. M. Microtubules suppress actomyosin-based cortical flow in Xenopus oocytes. J. Cell Sci. 110, 1907–1917 (1997).

    CAS  PubMed  Google Scholar 

  57. Kolodney, M. S. & Elson, E. L. Contraction due to microtubule disruption is associated with increased phosphorylation of myosin regulatory light chain. Proc. Natl Acad. Sci. USA 92, 10252–10256 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Bornens, M., Paintrand, M. & Celati, C. The cortical microfilament system of lymphoblasts displays a periodic oscillatory activity in the absence of microtubules: implications for cell polarity. J. Cell Biol. 109, 1071–1083 (1989).

    Article  CAS  PubMed  Google Scholar 

  59. Pletjushkina, O. J. et al. Induction of cortical oscillations in spreading cells by depolymerization of microtubules. Cell Motil. Cytoskeleton 48, 235–244 (2001).

    Article  CAS  PubMed  Google Scholar 

  60. Lampidis, T. J., Kolonias, D., Savaraj, N. & Rubin, R. W. Cardiostimulatory and antiarrhythmic activity of tubulin-binding agents. Proc. Natl Acad. Sci. USA 89, 1256–1260 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Paul, R. J., Bowman, P. S. & Kolodney, M. S. Effects of microtubule disruption on force, velocity, stiffness and [Ca2+](i) in porcine coronary arteries. Am. J. Physiol. Heart Circ. Physiol. 279, H2493–H2501 (2000).

    Article  CAS  PubMed  Google Scholar 

  62. Zhang, D., Jin, N., Rhoades, R. A., Yancey, K. W. & Swartz, D. R. Influence of microtubules on vascular smooth muscle contraction. J. Muscle Res. Cell Motil. 21, 293–300 (2000).

    Article  CAS  PubMed  Google Scholar 

  63. Koide, M. et al. Microtubule depolymerization normalizes in vivo myocardial contractile function in dogs with pressure-overload left ventricular hypertrophy. Circulation 102, 1045–1052 (2000).

    Article  CAS  PubMed  Google Scholar 

  64. Wang, N. et al. Mechanical behavior in living cells consistent with the tensegrity model. Proc. Natl Acad. Sci. USA 98, 7765–7770 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Ingber, D. E. Cellular tensegrity: defining new rules of biological design that govern the cytoskeleton. J. Cell Sci. 104, 613–627 (1993).

    PubMed  Google Scholar 

  66. Elbaum, M., Kuchnir Fygenson, D. & Libchaber, A. Buckling microtubules in vesicles. Phys. Rev. Lett. 76, 4078–4081 (1996).

    Article  CAS  PubMed  Google Scholar 

  67. Felgner, H., Frank, R. & Schliwa, M. Flexural rigidity of microtubules measured with the use of optical tweezers. J. Cell Sci. 109, 509–516 (1996).

    CAS  PubMed  Google Scholar 

  68. Elbaum, M., Chausovsky, A., Levy, E. T., Shtutman, M. & Bershadsky, A. D. Microtubule involvement in regulating cell contractility and adhesion-dependent signalling: a possible mechanism for polarization of cell motility. Biochem. Soc. Symp. 65, 147–172 (1999).

    CAS  PubMed  Google Scholar 

  69. Ren, Y., Li, R., Zheng, Y. & Busch, H. Cloning and characterization of GEF-H1, a microtubule-associated guanine nucleotide exchange factor for Rac and Rho GTPases. J. Biol. Chem. 273, 34954–34960 (1998).

    Article  CAS  PubMed  Google Scholar 

  70. van Horck, F. P., Ahmadian, M. R., Haeusler, L. C., Moolenaar, W. H. & Kranenburg, O. Characterization of p190RhoGEF, a RhoA-specific guanine nucleotide exchange factor that interacts with microtubules. J. Biol. Chem. 276, 4948–4956 (2001).

    Article  CAS  PubMed  Google Scholar 

  71. Ren, X. D., Kiosses, W. B. & Schwartz, M. A. Regulation of the small GTP-binding protein Rho by cell adhesion and the cytoskeleton. EMBO J. 18, 578–585 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Fukata, Y., Amano, M. & Kaibuchi, K. Rho–Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells. Trends Pharmacol. Sci. 22, 32–39 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. Bershadsky, A. D., Vaisberg, E. A. & Vasiliev, J. M. Pseudopodial activity at the active edge of migrating fibroblast is decreased after drug-induced microtubule depolymerization. Cell Motil. Cytoskeleton 19, 152–158 (1991).

    Article  CAS  PubMed  Google Scholar 

  74. Dunn, G. A., Zicha, D. & Fraylich, P. E. Rapid, microtubule-dependent fluctuations of the cell margin. J. Cell Sci. 110, 3091–3098 (1997).

    CAS  PubMed  Google Scholar 

  75. Waterman-Storer, C. M., Worthylake, R. A., Liu, B. P., Burridge, K. & Salmon, E. D. Microtubule growth activates Rac1 to promote lamellipodial protrusion in fibroblasts. Nature Cell Biol. 1, 45–50 (1999).

    Article  CAS  PubMed  Google Scholar 

  76. Bretscher, M. S. & Aguado-Velasco, C. Membrane traffic during cell locomotion. Curr. Opin. Cell Biol. 10, 537–541 (1998).

    Article  CAS  PubMed  Google Scholar 

  77. Toomre, D., Keller, P., White, J., Olivo, J. C. & Simons, K. Dual-color visualization of trans-Golgi network to plasma membrane traffic along microtubules in living cells. J. Cell Sci. 112, 21–33 (1999).

    CAS  PubMed  Google Scholar 

  78. Bershadsky, A. D. & Futerman, A. H. Disruption of the Golgi apparatus by brefeldin A blocks cell polarization and inhibits directed cell migration. Proc. Natl Acad. Sci. USA 91, 5686–5689 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Rodionov, V. I. et al. Microtubule-dependent control of cell shape and pseudopodial activity is inhibited by the antibody to kinesin motor domain. J. Cell Biol. 123, 1811–1820 (1993).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank O. Krylyskina and G. Resch for their invaluable help with the videos and animation. A.B. and B.G. are grateful to D. Riveline and J. Kirchner for providing the experimental data for figures 2 and 3. A. Huttenlocher is acknowledged for providing the DsRed zyxin construct that was used in figure 5. This work was supported in part by a grant from the Austrian Science Research Council to J.V.S. and I.K. B.G. is the incumbent of the E. Neter Chair in Cell and Tumor Biology; A.B. holds the J. Moss Chair of Biomedical Research.

Author information

Authors and Affiliations

  1. the Institute of Molecular Biology, Austrian Academy of Sciences, Billrothstrasse 11, Salzburg, 5020, Austria

    J. Victor Small & Irina Kaverina

  2. the Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, 76100, Israel

    Benjamin Geiger & Alexander Bershadsky

Authors
  1. J. Victor Small
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Benjamin Geiger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Irina Kaverina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alexander Bershadsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Victor Small.

Supplementary information

Online Video 1

A time-lapse video of a goldfish fibroblast that was expressing green fluorescent protein (GFP)–actin (green) and that was also micro-injected with rhodamine-tagged vinculin (red) to mark adhesion complexes (corresponding to Fig. 1). The inset movies correspond to the boxed areas I and IV in Fig. 1. Video 1.1 corresponds to boxed area I, which is shown in Fig. 1b,c and Fig. 2a, and shows newly forming adhesions. Video 1.2 corresponds to the boxed area IV in Fig. 2c and shows sliding, trailing adhesions. The time between frame-pairs in the Quick-Time videos is 60 s for video 1 and 30 s for videos 1.1 and 1.2; the interval between the sequential frames in the GFP and rhodamine channels is 1 s. The online video was provided by O. Krylyshkina. (MOV 128 kb)

Online Video 1.1

Video 1.1 corresponds to boxed area I, which is shown in Fig. 1b,c and Fig. 2a, and shows newly forming adhesions. (MOV 4046 kb)

Online Video 1.2

Video 1.2 corresponds to the boxed area IV in Fig. 2c and shows sliding, trailing adhesions. The time between frame-pairs in the Quick-Time videos is 60 s for video 1 and 30 s for videos 1.1 and 1.2; the interval between the sequential frames in the GFP and rhodamine channels is 1 s. (MOV 5598 kb)

Online Video 2

The targeting of substrate adhesion complexes by microtubules is shown (corresponding to Fig. 5). The video shows a peripheral region of a goldfish fibroblast thatwas transfected with green fluorescent protein–tubulin (green) and DsRed–zyxin (red). The time between frame-pairs was 10 s, with 1 s between the two fluorescent channels in one pair. The targeting events are circled in arrested frames and the inset movies show specific details. Video 2.1 highlights the multiple targeting of one focal adhesion by several microtubules (circled events), as well as the re-routing of one microtubule away from this adhesion to more peripheral adhesions (asterisk). Video 2.2 shows the dissolution of two focal adhesions (circled) after several targeting events. (MOV 513 kb)

Online Video 2.1

Video 2.1 highlights the multiple targeting of one focal adhesion by several microtubules (circled events), as well as the re-routing of one microtubule away from this adhesion to more peripheral adhesions (asterisk). (MOV 11190 kb)

Online Video 2.2

Video 2.2 shows the dissolution of two focal adhesions (circled) after several targeting events. (MOV 5095 kb)

Online Video 3

An animation depicting the salient features of the interactions between microtubules and sites of substrate adhesion. In a migrating cell, protrusion is supported by the formation of focal complexes at the cell front, which can then develop into focal adhesions. the cell rear is limited by focal adhesions that originate through the retraction of former regions of protrusion. Targeting of focal adhesions by microtubules is presumed to be associated with the transmission of a signal (orange stars) that promotes events leading to adhesion disassembly. Targeting of focal adhesions behind the cell front is required to promote adhesion turnover and facilitate further protrusion. Targeting of focal adhesions at the rear is more frequent and is required to promote adhesion release during retraction. The animation programme does not allow a realistic simulation of microtubule dynamics. Provided by G. Resch, Austrian Academy of Science, Austria. (MOV 6402 kb)

41580_2002_BFnrm971_MOESM8_ESM.jpg

Online figure 1 | Microtubule disruption induces stress fibre growth. The activation of actin stress-fibre assembly (right panels) in starved fibroblasts after the initiation of microtubule depolymerization by nocodazole (left panels) is shown. Reproduced with permission from Ref. 25 © (2002) Elsevier Science. (JPG 43 kb)

41580_2002_BFnrm971_MOESM9_ESM.jpg

Online figure 2 | Repetitive targeting of peripheral focal adhesins precedes cell-edge retraction. An example of the multiple targeting of a peripheral adhesion site by microtubules that leads to adhesion translocation and detachment. The panels show video sequences from the periphery of a goldfish fibroblast that was injected with Cy-3-tagged tubulin and rhodamine-tagged vinculin. Times are in minutes and seconds. Different adhesion sites are targeted at different time points, and the frames were selected for the targeting events of one adhesion. Reproduced with permission from Ref. 31 © (2002) The Rockefeller University Press. (JPG 23 kb)

41580_2002_BFnrm971_MOESM10_ESM.jpg

Online figure 3 | Microtubule polymerization dynamics are influenced by mechanical stress in the actin cytoskeleton. The feedback regulation of microtubules by the actin cytoskeleton. Transient relaxation of peripheral contractility induces microtubule depolymerization. A fish fibroblast that was transfected with green fluorescent protein–tubulin (green) and micro-injected with rhodamine-tagged vinculin (red) was exposed for 2–3 min on one edge to the myosin relaxant, ML-7, which was delivered through a micropipette. The first two panels show images before and after application. After removal of the drug (recovery), microtubules repolymerize to the cell edge and target adhesion sites (panel 3). Modified with permission from Ref. 19 © (2002) The Company of Biologists Ltd. (JPG 26 kb)

Related links

Related links

DATABASES

Swiss-Prot

Cdc42

Dia1

Rho kinase

Rights and permissions

Reprints and permissions

About this article

Cite this article

Small, J., Geiger, B., Kaverina, I. et al. How do microtubules guide migrating cells?. Nat Rev Mol Cell Biol 3, 957–964 (2002). https://doi.org/10.1038/nrm971

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm971

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing