Rho proteins crosstalk via RhoGDIalpha: At random or hierarchically ordered?

The small GTPases of the Rho family are key signaling molecules regulating a plethora of biological pathways. They can exert diverse, sometimes opposite, contributions to specific cellular processes explaining why their regulation and their crosstalk must be finely tuned. Several mechanisms driving crosstalk between Rho GTPases have been described in the literature. They implicate proteins regulating their activity or common downstream effectors. Among the proteins regulating Rho GTPases cycling, RhoGDIs were viewed until very recently as passive inhibitors. Here, we will focus on recent data supporting a role for RhoGDIalpha in the crosstalk between RhoGTPases and present our results suggesting that "preferential" RhoGDIalpha-mediated crosstalk takes place between closely related Rho GTPases.