Small GTPases in axon outgrowth.

We propose that small GTPases in the Rho/Rac/Cdc42 subfamily play a central role in signaling pathways from cell surface receptors to actin cytoskeleton changes in the growth cone. The proposal is based upon the following evidence. First, the Rho/Rac/Cdc42 subfamily GTPases have been shown to regulate various aspects of cytoskeletal organization from budding yeast to mammalian fibroblasts. Second, perturbation of GTPase activities of Rac and Cdc42 in neurons by constitutively active and dominant negative mutants results in specific defects in axon and dendrite outgrowth. In addition to reviewing existing experimental evidence, we will discuss the implications of such a model and the potential relationship with other signaling pathways.