Figure 7.

Model for the control of cell migration by integrin-specific regulation of Rho GTPases. Adhesion by β1 integrins promotes strong Rho/Rho kinase signaling. This counteracts three important parameters of persistent cell migration: (1) Rac-mediated lamellipodia formation; (2) development of static cell–matrix adhesions; and (3) cofilin-mediated actin cytoskeletal reorganization. As a result, β1 integrins promote a random mode of migration. Inhibition of Rho/Rho kinase signaling relieves the suppression of all three aspects and causes a switch from β1- to β3-associated behavior. Conversely, increased Rho signaling in cells adhering by αvβ3 triggers a conversion to β1-associated behavior. Increased Rac signaling can also stimulate a partial conversion from β1- to β3-associated behavior with increased lamellipodia formation and stabilization of cell–matrix adhesions. However, this does not lead to increased cofilin activity and hence, does not stimulate persistence.