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Vol. 17, Issue 5, 2377-2390, May 2006

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Rac1-null Mouse Embryonic Fibroblasts Are Motile and Respond to Platelet-derived Growth Factor

Luis Vidali ^*, Feng Chen , Gregor Cicchetti ^*, Yasutaka Ohta ^*, and David J. Kwiatkowski ^*

^* Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Department of Genetics, Children's Hospital Boston, Boston, MA 02115

Submitted October 14, 2005; Revised January 30, 2006; Accepted February 27, 2006
Monitoring Editor: Mark Ginsberg

Previous studies of Rac1 in fibroblasts have used dominant negative constructs, which may have nonspecific effects. We used a conditional Rac1 allele to critically examine Rac1 function in mouse fibroblasts. Lack of Rac1 had dramatic effects on nonconfluent cells, which were elongated and had extensive blebbing, but no lamellipodia or ruffle formation. However, Rac1-null fibroblasts translocated using pseudopodia-like protrusions without lamellipodia, migrating toward a platelet-derived growth factor (PDGF) gradient as efficiently as their wild-type counterparts. Rac1-null fibroblasts closed wounds in vitro and spread on a fibronectin substrate, although at a slower rate than wild-type cells. However, Rac1-null cells were markedly impaired in proliferation, with a defect in G1 to S transition, although they were capable of surviving in culture for more than 2 wk. These results refine our understanding of the functions of Rac1, indicate that lamellipodia formation is not required for cell motility, and show that PDGF-induced chemotaxis can occur in the absence of both lamellipodia and Rac1.

Abbreviations used: HTNC, histidine-TAT-nuclear localization-cre fusion peptide; MEF, mouse embryonic fibroblast; PDGF, platelet-derived growth factor; PI, propidium iodide.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Luis Vidali (lvidali{at}gmail.com) or David J. Kwiatkowski (dk{at}rics.bwh.harvard.edu).

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