Netrin-1 trafficking in human neurons

The secreted guidance cue netrin-1 orchestrates essential nervous system developmental processes such as axon pathfinding and synaptogenesis. However, little is known about the expression, transport, and localization of netrin-1 in human neurons. After optimizing human neuronal cultures derived from induced pluripotent stem cells (iPSC), I investigated the localization and intracellular transport of netrin-1. I demonstrated endogenous expression of netrin-1 within human iPSC-derived neurons via immunocytochemistry. I then studied the transport of fluorescently-labeled netrin-1 (netrin-1-mRuby3) via live cell imaging where netrin-1 traffics bidirectionally in neurons. Additionally, netrin-1 co-transports and co-localizes with the resident dense core vesicle protein chromogranin and KIF1A, the primary microtubule-based motor responsible for transport of this vesicle type. These findings are significant in the understanding of mechanisms behind netrin-1 function and regulation in human neurons.