The on-off relationship of Rho and Rac during integrin-mediated adhesion and cell migration.

Rho GTPases play an essential role in regulating cell spreading, adhesion, and migration downstream of integrin engagement with the extracellular matrix. In this review, we focus on RhoA and Rac1--2 Rho GTPases that are required for efficient adhesion and migration--and describe how specific guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) regulate the extensive crosstalk that exists between them. In particular, we assess the role of GEFs and GAPs in light of recent, unexpected evidence concerning the spatiotemporal relationship between RhoA and Rac1 at the leading edge of migrating cells. Force is increasingly recognized as a key regulator of cell adhesion and we highlight the role of GEFs and GAPs in mechanotransduction, before debating the controversial role of tension in focal adhesion maturation.