Small GTPase RhoG is a key regulator for neurite outgrowth in PC12 cells

The Rho family of small GTPases has been implicated in cytoskeletal reorgan ization and subsequent morphological changes in various cell types. Among t hem, Rac and Cdc42 have been shown to be involved in neurite outgrowth in n euronal cells. In this study, we examined the role of RhoG, another member of Rho family GTPases, in nerve growth factor (NGF)-induced neurite outgrow th in PC12 cells. Expression of wild-type RhoG in PC12 cells induced neurit e outgrowth in the absence of NGF, and the morphology of wild-type RhoG-exp ressing cells was similar to that of NGF-differentiated cells. Constitutive ly active RhoG-transfected cells extended short neurites but developed larg e lamellipodial or filopodial structures at the tips of neurites. RhoG-indu ced neurite outgrowth was inhibited by coexpression with dominant-negative Rac1 or Cdc42. In addition expression of constitutively active RhoG elevate d endogenous Rac1 and Cdc42 activities. We also found that the NGF-induced neurite outgrowth was enhanced by expression of wild-type RhoG whereas expr ession of dominant-negative RhoG suppressed the neurite outgrow th. Further more, constitutively active pas-induced neurite outgrowth was also suppress ed by dominant-negative RhoG. Taken together, these results suggest that Rh oG is a key regulator in NGF-induced neurite outgrowth, acting downstream o f Ras and upstream of Rac1 and Cdc42 in PC12 cells.