Regulating axon branch stability: The role of p190 RhoGAP in repressing a retraction signaling pathway

Mechanisms that regulate axon branch stability are largely unknown. Genome- wide analyses of Rho GTPase activating protein (RhoGAP) function in Drosoph ila using RNA interference identified p190 RhoGAP as essential for axon sta bility in mushroom body neurons, the olfactory learning and memory center. p190 inactivation leads to axon branch retraction, a phenotype mimicked by activation of GTPase RhoA and its effector kinase Drok and modulated by the level and phosphorylation of myosin regulatory light chain. Thus, there ex ists a retraction pathway from RhoA to myosin in maturing neurons, which is normally repressed by p190. Local regulation of p190 could control the str uctural plasticity of neurons. Indeed, genetic evidence supports negative r egulation of p190 by integrin and Src, both implicated in neural plasticity .