Abstract: Molecular motors drive the long-distance transport of organelles in neurons. This transport, driven by the microtubule motor proteins kinesin and cytoplasmic dynein, can move cargos over distances of more than a meter. Cargos transported by these motors include signaling endosomes, which mediate the signaling of neurotrophic signals from the cell periphery to the nucleus to mediate gene expression and promote neuronal development and survival. We are using live cell imaging in primary neurons, along with optogenetic approaches and single-molecule reconstitution assays, to explore the underlying mechanisms regulating the transport of signaling endosomes.