Dual function of rhoD in vesicular movement and cell motility

The trafficking of intracellular membranes requires the coordination of mem brane-cytoskeletal interactions. Rab proteins are key players in the regula tion of vesicular transport, while Rho family members control actin-depende nt cell functions. We have previously identified a rho protein, rhoD, which is localized to the plasma membrane and early endosomes. When overexpresse d, rhoD alters the actin cytoskeleton and plays an important role in endoso me organization. We found that a rhoD mutant exerts its effect on early end osome dynamics through an inhibition in organelle motility. In these studie s, the effect of rhoD on endosome dynamics was evaluated in the presence of a constitutively active, GTPase-deficient mutant of rab5, rab5Q79L. As rab 5Q79L itself stimulates endosome motility, rhoD might counteract this stimu lation, without itself exerting any effect in the absence of rab5 activatio n. We have now addressed this issue by investigating the effect of rhoD in the absence of co-expressed rab5. We find that rhoDG26V alone alters vesicu lar dynamics. Vesicular movement, in particular the endocytic/recycling circuit, is alter ed during processes such as cell motility, Due to the participation of vesi cular motility and cytoskeletal rearrangements in cell movement and the inv olvement of rhoD in both, we have addressed the role of rhoD in this proces s and have found that rhoDG26V inhibits endothelial cell motility.