SMALL GTPASES IN AXON OUTGROWTH

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