Drerup Lab

In neurons, retrograde transport is the process by which cargos, including trophic factors, organelles, cytoskeletal elements, and many others are carried toward microtubule minus ends in axons. During axon development, retrograde transport of signaling endosomes is essential for axon outgrowth. Similarly, retrograde transport of injury signals has been linked to degenerative events, tying retrograde axonal transport to establishment, maintenance, and regeneration of neural circuits. Retrograde axonal transport is accomplished primarily by the single Cytoplasmic dynein 1 motor protein complex. Perhaps not surprisingly, defects in dynein-dependent cargo transport in neurons have been associated with neurodegenerative diseases ranging from Charcot-Marie-Tooth disease to Parkinson’s and Amyotrophic Lateral Sclerosis. Therefore, there is great interest in understanding how this motor binds cargos and moves them at the right time to the right place.

To better understand dynein function, we have developed novel tools and techniques to address the mechanisms of retrograde cargo transport. First, we optimized techniques to image axonal transport and microtubule dynamics in vivo using the zebrafish. Second, we designed a forward genetic screen to identify adaptor proteins for dynein-dependent cargo transport. Third, we optimized in vivo functional imaging to determine how disruption of cargo transport effects neural circuit function. Together, we are using these tools and techniques to work further our understanding of the cellular and molecular mechanisms governing retrograde transport and how disrupting this process impacts neural circuit structure and function.