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In this study, we investigated the role of Rap1 in axonal growth and its activation in response to neurotrophins and myelin\u2010associated inhibitors. We report that Rap1 is activated by brain\u2010derived neurotrophic factor and that this activation can be blocked by myelin\u2010associated glycoprotein (MAG) or central nervous system myelin, which also induced increases in Rap1GAP1 levels. In addition, we demonstrate that adenoviral overexpression of Rap1 enhances neurite outgrowth in the presence of MAG and myelin, while inhibition of Rap1 activity through overexpression of Rap1GAP1 blocks neurite outgrowth. 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