Actin (white) forms membrane ruffles when ROCK is blocked (right).

Directional migration of a cell requires both lamellipodia formation at the leading edge and actomyosin contraction within the tail. New results from Tsuji et al. (page 819) indicate that Rho may mediate both tasks, and that these two arms of Rho signaling are antagonistic.

Rho signaling is known to mediate the formation of stress fibers, structures similar to actin bundles that are required for tail retraction. This function of Rho requires the effector kinase ROCK. The new results demonstrate that Rho can also signal through a different effector, mDia1, and cause membrane ruffling. The mDia1 pathway activated another Rho family GTPase member, Rac. In neuronal cells, Rho inhibits Rac, but this is the first demonstration that Rho can also activate Rac.

Tsuji et al. uncovered mDia1- mediated membrane ruffling by selectively inhibiting ROCK signaling. Thus, the ROCK pathway normally antagonizes the mDia1/Rac pathway. Opposing effects of Dia and ROCK have also been demonstrated recently by Sahai and Marshall (Sahai, E., and C.J. Marshall. 2002 Nat. Cell Biol. 10.1038/ncb796). Basal levels of GTP-Rho may be sufficient to activate mDia1, whereas high concentrations of active Rho are probably required to mediate ROCK-dependent signaling. In motile cells, actomyosin contraction and lamellipodium formation probably require differentially controlled local concentrations of active Rho. ▪