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Abstract
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.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
C.D.L. is grateful to the US. Army Medical Research and Materiel Command for a Breast Cancer Research Program Postdoctoral Fellowship Award (W81XWH-14-1-0033). K.B. thanks the Kenan Foundation and the National Institutes of Health (Grant GM029860) for support.