Chimaerins act downstream from neurotrophins in overcoming the inhibition of neurite outgrowth produced by myelin-associated glycoprotein

Several myelin-derived proteins are inhibitory cues that contribute to the lack of regeneration of the CNS and inhibit neurite outgrowth from some neurons in vitro. This inhibition is blocked if neurons are exposed to neurotrophins before encountering the inhibitors. Here, we demonstrate that chimaerin, one of the Rho GTPase activating proteins, is transcriptionally up-regulated after exposure to neurotrophins in post-natal cerebellar neurons. The expression of alpha chimaerin in the cerebellum is developmentally correlated with the abolishment of the inhibitory effect of myelin-associated glycoprotein (MAG). Ectopic expression of alpha chimaerin in cerebellar neurons results in resistance to MAG in regard to neurite outgrowth. These results suggest that up-regulated expression of chimaerin counteracts the activation of RhoA, which is a key molecule in transducing inhibitory signals in neurons.