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Vol. 16, Issue 10, 4473-4484, October 2005
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* Heisenberg Group "Regulation of Cytoskeletal Organization," Max Planck Institute of Biochemistry, 82152 Martinsried, Germany;
Molecular Cell Biology Unit, Department for Molecular Biomedical Research, VIB-Ghent University, 9000 Ghent, Belgium;
Institute of Stem Cell Research, GSF-National Research Center for Environment and Health, 85764 Neuherberg, Germany;
Mucosal Immunity Group, German Research Centre for Biotechnology, 38124 Braunschweig, Germany; and
|| Cytoskeleton Dynamics Group, German Research Centre for Biotechnology, 38124 Braunschweig, Germany
Submitted January 24, 2005;
Revised July 5, 2005;
Accepted July 6, 2005
Monitoring Editor: Mark Ginsberg
Cdc42 is a small GTPase involved in the regulation of the cytoskeleton and cell polarity. To test whether Cdc42 has an essential role in the formation of filopodia or directed cell migration, we generated Cdc42-deficient fibroblastoid cells by conditional gene inactivation. We report here that loss of Cdc42 did not affect filopodium or lamellipodium formation and had no significant influence on the speed of directed migration nor on mitosis. Cdc42-deficient cells displayed a more elongated cell shape and had a reduced area. Furthermore, directionality during migration and reorientation of the Golgi apparatus into the direction of migration was decreased. However, expression of dominant negative Cdc42 in Cdc42-null cells resulted in strongly reduced directed migration, severely reduced single cell directionality, and complete loss of Golgi polarization and of directionality of protrusion formation toward the wound, as well as membrane blebbing. Thus, our data show that besides Cdc42 additional GTPases of the Rho-family, which share GEFs with Cdc42, are involved in the establishment and maintenance of cell polarity during directed migration.
The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).
Address correspondence to: Cord Brakebusch (brakebus{at}biochem.mpg.de).
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