The Rho family GTPases Rac and Cdc42 are both crucial to directional cell migration, but their individual contributions to this process are less clear. On page 2971, James Bear and colleagues use cellular optogenetics to investigate the specific roles of Rac and Cdc42 signalling in directed migration. By using an improved light-inducible dimer (iLID) system, the authors find that differentially stimulating Rac and Cdc42 on a fibronectin substrate is sufficient to spatially regulate lamellipodia protrusion and directed migration. They term the directional cell migration induced by spatially biased GTPase activity ‘optotaxis’. Arp2/3 is also found to be necessary for both Rac- and Cdc42-induced lamellipodia and optotaxis. Rac activation is shown to be insufficient to produce stable lamellipodia or directional migration in the absence of exogenous fibronectin. Cdc42 activation, however, can induce a stable protrusion in the absence of exogenous fibronectin because it induces deposition of cellular fibronectin; it also requires integrin binding and myosin contractility. These data demonstrate that the activity of Rac and Cdc42 is sufficient to drive directed cell migration. The authors propose that by depositing fibronectin as the cell protrudes, the cell reinforces and supports its own protrusion and facilitates directed migration.
