Cell migration involves the generation of protrusions, such as membrane ruffles and lamellipodia, which help cells to explore the surrounding space and to initiate nascent adhesions. Lamellipodia consist of networks of connected actin filaments that are mediated by the actin nucleator Arp2/3. Small GTPases of the Rac family are known to stimulate lamellipodia formation, but their exact role is unclear because, thus far, only conditional Rac1-knockout cell lines have been established. In this study (p. 4572), Klemens Rottner and colleagues generate the first permanent fibroblast cell lines that are genetically deficient for Rac1, and also lack detectable levels of haematopoietic Rac2 and brain-specific Rac3. They find that these Rac-deficient cells are devoid of lamellipodia; however, these can be restored by expression of Rac, but not of RhoG or Cdc42, which had previously been implicated in driving lamellipodia formation. In addition, the Rac-deficient cells also show a strong reduction in wound closure and random cell migration. Surprisingly, however, these cells are able to spread despite the absence of lamellipodia, suggesting that Rac signalling is dispensable for actin remodelling events at the cell periphery that drive the protrusion of filopodia and the formation of nascent adhesions. These findings further highlight that the Rac-deficient cell lines presented here are useful tools in dissecting the functions of Rac in the diverse cellular processes they are involved in.

• © 2013. Published by The Company of Biologists Ltd