Figure 10.

A Rac1-dependent redox rheostat regulates growth cone motility in response to extrinsic stimuli. Exposure of neuronal growth cones either to TNFα or to IL-1β rapidly stimulates ROS generation through NOX activity under the regulation of the small GTPase Rac1 and concomitant paralysis and degeneration of morphology of growth cones. Moreover, growth cone motility is not only sensitive to the overabundance of ROS either via NOX activation or via constitutive Rac1 activity (Rac1^V12) but is also impaired by a substantial depletion of ROS (antioxidants) or inhibition of Rac1 activity (Rac1^N17). Consequently, productive growth cone motility requires an optimal concentration of intracellular ROS generated by a Rac1-regulated NOX activity. It is plausible that this Rac1/NOX-redox rheostat is responsive to many extrinsic stimuli including cytokines, growth factors, hormones, and cell adhesion molecules for which redox signaling mechanism has been demonstrated.