Grant: Project Grant

Huntingtin links cargoes to the motor proteins that move them around the cell. Huntingtin interacts with the motor protein kinesin that transports cargoes to the cell periphery, dynein that moves to the cell center, and myosin-VI that tethers cargoes near the cell membrane. Huntingtin associates with many different cargoes involved in both signalling and degradation, and is expressed in most types of cells. Mutations to huntingtin result in neurodegenerative disease, where the age of onset and the severity correspond to the length of the disease-causing polyglutamine expansions. We have developed tools to measure the number and types of motor proteins bound to intracellular cargoes, the forces they exert, and their motility with single-molecule resolution. We will apply these tools to neurons engineered to express huntingtin polyglutamine expansions of different lengths to uncover how huntingtin controls the motor proteins that drive transport, and how mutations disrupt transport to cause neurodegenerative disease.