Regulation of the molecular motor kinesin-1

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DESCRIPTION (provided by applicant): Motor proteins carry cellular cargoes along the cytoskeleton to their destination. Disregulation of these processes underlies a number of diseases ranging from cancer to polycystic kidney disease to neurodegenerative diseases. The long-term goal of our research is to understand how motor protein transport is controlled and coordinated in cells. We will use molecular, biochemical and cell biological analyses to address the mechanisms that control cargo binding and motor activity of the microtubule-based motor kinesin-1. Our hypothesis is that spatially segregated protein complexes control kinesin-1 transport at the point of departure and at the destination. We will analyze the mechanisms by which cargo binding leads to motor activation at the point of departure. We will explore the possibility that modifications of the microtubule cytoskeleton play a role in directing motor protein transport to the correct cellular destination. We will analyze the role of newly-identified protein complexes in the release of cargo and inactivation of kinesin-1 at the destination. This work will provide exciting new insights into the function of kinesin-1 in nerve cells. This work will also increase our understanding of how the regulation of motor proteins gives rise to coordinated transport of protein complexes in cells and will suggest therapeutic targets in human disease.