This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Monypenny, J. Articles by Watanabe, N. Search for Related Content PubMed PubMed Citation Articles by Monypenny, J. Articles by Watanabe, N.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2009, p. 2730-2747, Vol. 29, No. 10
0270-7306/09/$08.00+0     doi:10.1128/MCB.01285-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Cdc42 and Rac Family GTPases Regulate Mode and Speed but Not Direction of Primary Fibroblast Migration during Platelet-Derived Growth Factor-Dependent Chemotaxis ^,

James Monypenny,^1* Daniel Zicha,² Chiharu Higashida,¹ Fabian Oceguera-Yanez,¹ Shuh Narumiya,¹ and Naoki Watanabe¹

Department of Pharmacology, Kyoto University Faculty of Medicine, Yosida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan,¹ Light Microscopy Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom²

Received 13 August 2008/ Returned for modification 20 October 2008/ Accepted 19 February 2009

Cdc42 and Rac family GTPases are important regulators of morphology, motility, and polarity in a variety of mammalian cell types. However, comprehensive analysis of their roles in the morphological and behavioral aspects of chemotaxis within a single experimental system is still lacking. Here we demonstrate using a direct viewing chemotaxis assay that of all of the Cdc42/Rac1-related GTPases expressed in primary fibroblasts, Cdc42, Rac1, and RhoG are required for efficient migration towards platelet-derived growth factor (PDGF). During migration, Cdc42-, Rac1-, and RhoG-deficient cells show aberrant morphology characterized as cell elongation and cell body rounding, loss of lamellipodia, and formation of thick membrane extensions, respectively. Analysis of individual cell trajectories reveals that cell speed is significantly reduced, as well as persistence, but to a smaller degree, while the directional response to the gradient of PDGF is not affected. Combined knockdown of Cdc42, Rac1, and RhoG results in greater inhibition of cell speed than when each protein is knocked down alone, but the cells are still capable of migrating toward PDGF. We conclude that, Cdc42, Rac1, and RhoG function cooperatively during cell migration and that, while each GTPase is implicated in the control of morphology and cell speed, these and other Cdc42/Rac-related GTPases are not essential for the directional response toward PDGF.

---

* Corresponding author. Mailing address: Cell Motility and Cytoskeleton Group, Randall Division of Cell and Molecular Biophysics, King's College London, Guy's Campus, London SE1 1UL, United Kingdom. Phone: 44(0)20 7848 6454. Fax: 44 (0)20 7848 6435. E-mail: james.monypenny_of_pitmilly{at}kcl.ac.uk

Published ahead of print on 9 March 2009.

Supplemental material for this article may be found at http://mcb.asm.org/.

---

Molecular and Cellular Biology, May 2009, p. 2730-2747, Vol. 29, No. 10
0270-7306/09/$08.00+0     doi:10.1128/MCB.01285-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Lai, F. P.L., Szczodrak, M., Oelkers, J. M., Ladwein, M., Acconcia, F., Benesch, S., Auinger, S., Faix, J., Small, J. V., Polo, S., Stradal, T. E.B., Rottner, K. (2009). Cortactin Promotes Migration and Platelet-derived Growth Factor-induced Actin Reorganization by Signaling to Rho-GTPases. Mol. Biol. Cell 20: 3209-3223 [Abstract] [Full Text]