Regulation of Microtubules by Rho GTPases in Migrating Cells

  1. Gregory Bock Organizer and
  2. Jamie Goode
  1. Gregg G. Gundersen1,
  2. Ying Wen2,
  3. Christina H. Eng2,
  4. Jan Schmoranzer2,
  5. Noemi Cabrera-Poch2,
  6. Edward J. S. Morris2,
  7. Michael Chen2 and
  8. Edgar R. Gomes2

Published Online: 7 OCT 2008

DOI: 10.1002/047001766X.ch10

Signalling Networks in Cell Shape and Motility: Novartis Foundation Symposium 269

Signalling Networks in Cell Shape and Motility: Novartis Foundation Symposium 269

How to Cite

Gundersen, G. G., Wen, Y., Eng, C. H., Schmoranzer, J., Cabrera-Poch, N., Morris, E. J. S., Chen, M. and Gomes, E. R. (2005) Regulation of Microtubules by Rho GTPases in Migrating Cells, in Signalling Networks in Cell Shape and Motility: Novartis Foundation Symposium 269 (eds G. Bock and J. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/047001766X.ch10

Author Information

  1. 1

    Department of Anatomy and Cell Biology, Columbia University, 1217 Black Building, 630 West 168th Street, New York, NY 10032, USA

  2. 2

    Departments of Anatomy & Cell Biology and Pathology, Columbia University, 630 W. 168th Street, New York, NY 10032, USA

Publication History

  1. Published Online: 7 OCT 2008
  2. Published Print: 9 SEP 2005

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470011904

Online ISBN: 9780470017661

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Keywords:

  • microtubules (MTs);
  • MT organizing centre (MTOC);
  • rearward nuclear movement;
  • MT stabilization;
  • serum-starved monolayers;
  • MT stabilization pathway;
  • Rho GTPases and formins;
  • EB1 in MT stabilization;
  • conventional epifluorescence microscopy;
  • actin–myosin rearward flow

Summary

Microtubules (MTs) contribute to cell polarization and migration, but the molecular mechanism involved are unknown. We have explored signalling pathways that generate specific changes in MTs arrays in wounded monolayers of fibroblasts. In earlier work, we found that Rho GTPase and its effector mDia, stimulate selective MT stabilization in the lamella, whereas Cdc42 and the MTmotor protein dynein regulate MT organizing centre (MTOC) reorientation towards the leading edge. We have now found that the MT tip proteins EB1 and adenomatous polyposis coli protein (APC) function with mDia to stabilize MTs and interact directly with mDia. EB1, APC and mDia localize to the ends of stabilized MTs suggesting that they may contribute to capping of these MTs. Models of MTOC reorientation suggest that the MTOC moves in front of the nucleus by dynein pulling on MTs. In contrast, we find by directly imaging MTOC reorientation that the nucleus moves rearward while the MTOC remains stationary. Rearward nuclear movement is coupled to retrograde actin-myosin flow and is regulated by Cdc42 and its effector myotonic dystrophy kinase-related Cdc42-binding kinase. Dynein is not involved in nuclear movement, but is essential to maintain the MTOC at the cell centroid. These results show that there are two Cdc42 pathways that regulate MTOC reorientation.