The axon guidance cue netrin-1 and its receptor DCC promote axon branching in developing cortical neurons. In this study, we detail a novel molecular mechanism by which the brain-enriched E3 ubiquitin ligase TRIM9 orchestrates multimerization of DCC, requisite activation of FAK and Src family kinases, and increases in exocytic vesicle fusion, all during netrin-dependent neuronal morphogenesis. We are the first to show that non-degradative ubiquitination of a receptor alters kinase activation and signaling pathways during morphogenesis.
