Rho family GTPases, including RAC1, RHOA, and CDC42, are ideal candidates to regulate aspects of cytoskeletal dynamics downstream of axon guidance receptors. Biochemical and genetic studies have revealed an important role for CDC42 and RAC1 in ROBO repulsion. ROBO controls the activity of Rho GTPases by interacting with a family of SLIT/ROBO-specific GAPs (SrGAPs) and Vilse/CrossGAP. SrGAPs inactivate CDC42 and Vilse/CrossGAP specifically inactivates RAC1.
It was recently implicated that SRGAP3 may inactivate RAC1 downstream of SLIT1-activated ROBO2, which promotes neurite outgrowth in mammalian dorsal root ganglion (DRG) neurons (Zhang et al. 2014).