Crosstalk between microtubules and actin is essential for changes in cell morphology. Rho-family GTPases, such as Rho, Rac and Cdc42, regulate both systems and are therefore ideally positioned to relay this. On , Tod Smeal and co-workers describe one way they do so, showing that the kinase PAK4 is critical. PAKs are important Rho-family effectors but few of their targets are known. Smeal and co-workers now reveal that PAK4 (a Cdc42 effector) phosphorylates the guanine-nucleotide-exchange factor GEF-H1 (a Rho/Rac activator) and that the two form a complex on microtubules in vivo. The authors show that phosphorylation of Ser180 causes release of GEF-H1 from microtubules. Furthermore it blocks GEF-H1-dependent formation of actin stress fibres, promoting lamellipodial protrusion instead – reminiscent of Rac. When Ser180 is mutated, GEF-H1 by contrast induces stress fibres – reminiscent of Rho. The authors note that the mutant GEF-H1 retains GEF activity. They therefore conclude that PAK4 phosphorylation regulates the targeting rather than exchange activity of GEF-H1. Their findings are consistent with a model in which PAK4 acts both upstream and downstream of Rho-family GTPases and functions as a switch that links microtubules with different actin rearrangements.
