Interaction of RhoD and ZIP kinase modulates actin filament assembly and focal adhesion dynamics

RhoD is a member of the classical Rho GTPases and it has an essential role in the regulation of actin dynamics. Furthermore, RhoD also localizes to early endosomes and recycling endosomes, indicating additional roles in the regulation of endosome trafficking. A yeast two-hybrid screen identified Zipper-Interacting Protein Kinase (ZIPK) as a RhoD target. We found that RhoD interacts with ZIP kinase in a GTP dependent manner and modulates actin and focal adhesion reorganization. Interestingly, while ectopic expression of ZIPK in fibroblasts induces actin reorganization and actomyosin contraction seen as stress fiber bundling and membrane blebbing, the concomitant expression of active RhoD suppressed this phenotype. Previously, RhoD has been associated with focal adhesion regulation, and in line with this notion, we observed that ZIPK resulted in reorganization of focal adhesion and increased adhesion size. Importantly, the RhoD activity suppressed ZIPK-dependent effects on FAK activity, indicating a functional interplay between RhoD and FAK in the focal adhesion dynamics.

► RhoD has a role in actin dynamics that is distinct from RhoA, Rac1 and Cdc42.
► RhoD binds death-associated protein kinase member ZIPK in a GTP-dependent manner.
► RhoD suppresses the ZIPK-dependent effects on stress-fiber assembly.
► RhoD modulates ZIPK-induced focal adhesion reorganization and FAK activity.