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

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2006, p. 6844-6858, Vol. 26, No. 18
0270-7306/06/$08.00+0     doi:10.1128/MCB.00283-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The Rho-mDia1 Pathway Regulates Cell Polarity and Focal Adhesion Turnover in Migrating Cells through Mobilizing Apc and c-Src{dagger}

Norikazu Yamana,1,2,{ddagger} Yoshiki Arakawa,1,2,{ddagger},# Tomohiro Nishino,1 Kazuo Kurokawa,3,|| Masahiro Tanji,1,2 Reina E. Itoh,3 James Monypenny,1 Toshimasa Ishizaki,1 Haruhiko Bito,1,§ Kazuhiko Nozaki,2 Nobuo Hashimoto,2, Michiyuki Matsuda,3 and Shuh Narumiya1*

Department of Pharmacology,1 Department of Neurosurgery, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan,2 Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan3

Received 15 February 2006/ Returned for modification 13 March 2006/ Accepted 29 June 2006

Directed cell migration requires cell polarization and adhesion turnover, in which the actin cytoskeleton and microtubules work critically. The Rho GTPases induce specific types of actin cytoskeleton and regulate microtubule dynamics. In migrating cells, Cdc42 regulates cell polarity and Rac works in membrane protrusion. However, the role of Rho in migration is little known. Rho acts on two major effectors, ROCK and mDia1, among which mDia1 produces straight actin filaments and aligns microtubules. Here we depleted mDia1 by RNA interference and found that mDia1 depletion impaired directed migration of rat C6 glioma cells by inhibiting both cell polarization and adhesion turnover. Apc and active Cdc42, which work together for cell polarization, localized in the front of migrating cells, while active c-Src, which regulates adhesion turnover, localized in focal adhesions. mDia1 depletion impaired localization of these molecules at their respective sites. Conversely, expression of active mDia1 facilitated microtubule-dependent accumulation of Apc and active Cdc42 in the polar ends of the cells and actin-dependent recruitment of c-Src in adhesions. Thus, the Rho-mDia1 pathway regulates polarization and adhesion turnover by aligning microtubules and actin filaments and delivering Apc/Cdc42 and c-Src to their respective sites of action.

* Corresponding author. Mailing address: Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan. Phone: 81-75-753-4392. Fax: 81-75-753-4693. E-mail: snaru{at}mfour.med.kyoto-u.ac.jp.

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

{ddagger} N.Y. and Y.A. contributed equally to this work.

# Present address: Cell Motility Laboratory, Cancer Research UK, London WC2A 3PX, United Kingdom.

§ Present address: Department of Neurochemistry, University of Tokyo Graduate School of Medicine, Tokyo 113-0033, Japan.

|| Present address: Molecular Membrane Biology Laboratory, RIKEN Discovery Research Institute, Saitama 351-0198, Japan.

Present address: Department of Pathology and Biology of Diseases, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan.

Molecular and Cellular Biology, September 2006, p. 6844-6858, Vol. 26, No. 18
0270-7306/06/$08.00+0     doi:10.1128/MCB.00283-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nalbant, P., Chang, Y.-C., Birkenfeld, J., Chang, Z.-F., Bokoch, G. M. (2009). Guanine Nucleotide Exchange Factor-H1 Regulates Cell Migration via Localized Activation of RhoA at the Leading Edge. Mol. Biol. Cell 20: 4070-4082 [Abstract] [Full Text]  
  • Huveneers, S., Danen, E. H. J. (2009). Adhesion signaling - crosstalk between integrins, Src and Rho. J. Cell Sci. 122: 1059-1069 [Abstract] [Full Text]  
  • Senju, Y., Miyata, H. (2009). The Role of Actomyosin Contractility in the Formation and Dynamics of Actin Bundles During Fibroblast Spreading. J Biochem 145: 137-150 [Abstract] [Full Text]  
  • Hudson, B. I., Kalea, A. Z., del Mar Arriero, M., Harja, E., Boulanger, E., D'Agati, V., Schmidt, A. M. (2008). Interaction of the RAGE Cytoplasmic Domain with Diaphanous-1 Is Required for Ligand-stimulated Cellular Migration through Activation of Rac1 and Cdc42. J. Biol. Chem. 283: 34457-34468 [Abstract] [Full Text]  
  • Holeiter, G., Heering, J., Erlmann, P., Schmid, S., Jahne, R., Olayioye, M. A. (2008). Deleted in Liver Cancer 1 Controls Cell Migration through a Dia1-Dependent Signaling Pathway. Cancer Res. 68: 8743-8751 [Abstract] [Full Text]  
  • Bartolini, F., Moseley, J. B., Schmoranzer, J., Cassimeris, L., Goode, B. L., Gundersen, G. G. (2008). The formin mDia2 stabilizes microtubules independently of its actin nucleation activity. JCB 181: 523-536 [Abstract] [Full Text]  
  • Watanabe, S., Ando, Y., Yasuda, S., Hosoya, H., Watanabe, N., Ishizaki, T., Narumiya, S. (2008). mDia2 Induces the Actin Scaffold for the Contractile Ring and Stabilizes Its Position during Cytokinesis in NIH 3T3 Cells. Mol. Biol. Cell 19: 2328-2338 [Abstract] [Full Text]  
  • Goulimari, P., Knieling, H., Engel, U., Grosse, R. (2008). LARG and mDia1 Link G{alpha}12/13 to Cell Polarity and Microtubule Dynamics. Mol. Biol. Cell 19: 30-40 [Abstract] [Full Text]  
  • Carramusa, L., Ballestrem, C., Zilberman, Y., Bershadsky, A. D. (2007). Mammalian diaphanous-related formin Dia1 controls the organization of E-cadherin-mediated cell-cell junctions. J. Cell Sci. 120: 3870-3882 [Abstract] [Full Text]  
  • Gupton, S. L., Eisenmann, K., Alberts, A. S., Waterman-Storer, C. M. (2007). mDia2 regulates actin and focal adhesion dynamics and organization in the lamella for efficient epithelial cell migration. J. Cell Sci. 120: 3475-3487 [Abstract] [Full Text]  
  • Sakata, D., Taniguchi, H., Yasuda, S., Adachi-Morishima, A., Hamazaki, Y., Nakayama, R., Miki, T., Minato, N., Narumiya, S. (2007). Impaired T lymphocyte trafficking in mice deficient in an actin-nucleating protein, mDia1. JEM 204: 2031-2038 [Abstract] [Full Text]  
  • Eisenmann, K. M., West, R. A., Hildebrand, D., Kitchen, S. M., Peng, J., Sigler, R., Zhang, J., Siminovitch, K. A., Alberts, A. S. (2007). T Cell Responses in Mammalian Diaphanous-related Formin mDia1 Knock-out Mice. J. Biol. Chem. 282: 25152-25158 [Abstract] [Full Text]  
  • Kroboth, K., Newton, I. P., Kita, K., Dikovskaya, D., Zumbrunn, J., Waterman-Storer, C. M., Nathke, I. S. (2007). Lack of Adenomatous Polyposis Coli Protein Correlates with a Decrease in Cell Migration and Overall Changes in Microtubule Stability. Mol. Biol. Cell 18: 910-918 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»