The small GTPases Rac and Rho modulate migration speed and chemotaxis, with increased expression of Rac in lamellipodia correlating with increased velocity. In the current study, Pankov et al. found that reducing the total amount of Rac1 in a cell by 30% to 50% induced persistent movement and limited random walking. The reduction in Rac reduced the number of lamellae, leaving such structures only at the cell ends. By contrast, knocking down RhoA reduced the rate of migration but did not alter migration style.
Unlike chemotaxis, which also induces persistent movement, the newly identified Rac function did not require phosphatidylinositol 3′ kinase activity, indicating that the two methods of migration control are distinct. Rac activity was affected by the cell environment, however. Cells grown in two-dimensional tissue culture had more Rac and moved in a more random fashion than those grown in a three-dimensional matrix, even when the molecular composition of the two substrates was identical. Rac activity was also dependent on β1 integrin, as expected from previous studies.
Given the strength of Rac's influence, the authors speculate that such internal control of migration style might allow cells to switch between exploring their environment through random migration to moving as a group in one direction, as they do during wound healing and development. Now the trick will be to find tools that are sensitive enough to see such small changes in Rac levels in vivo, so that the hypothesis can be tested.