Grant: Project Grant

Motor proteins move along microtubule tracks to transport mRNA, proteins, organelles, and other cargoes in the cell. Two motor proteins, kinesin and dynein, are responsible for long-range transport. Kinesins move towards the cell periphery while dynein moves towards the cell center. These motors coordinate to transport cargoes in both directions along microtubules and enable navigation through the dense and crowded cellular environment. Defects in transport cause neurodegenerative and developmental disorders. For example, mutations in kinesin-1 and dynein result in the neurodegenerative diseases Hereditary Spastic Paraplegia and Charcot-Marie Tooth disease, and impaired transport is a hallmark of Amyotrophic Lateral Sclerosis, Alzheimer's disease, and Huntington's disease. While studies over the past two decades have identified the motor proteins that drive transport and how they generate movement, the mechanisms that regulate kinesin and dynein to control the direction of transport remain unclear. We hypothesize the scaffolding molecules that recruit motor proteins to cargoes play an important role in controlling their activity. We will employ powerful microscopy techniques that allow us to image single motor proteins with nanometer precision and measure the forces they exert to understand how motor proteins are turned on and off in the cell.