Regulation of the molecular motor kinesin-I

描述（由申请人提供）：马达蛋白沿着细胞骨架将细胞货物运送到其目的地。这些过程的失调是许多疾病的基础，从癌症到多囊肾病到神经退行性疾病。我们研究的长期目标是了解运动蛋白转运在细胞中是如何控制和协调的。我们将使用分子，生物化学和细胞生物学分析，以解决控制货物的结合和基于微管的运动驱动蛋白-1的运动活性的机制。我们的假设是，空间分离的蛋白质复合物控制驱动蛋白-1运输的出发点和目的地。我们将分析的机制，货物绑定导致电机激活的出发点。我们将探讨微管细胞骨架的修饰在指导马达蛋白运输到正确的细胞目的地中发挥作用的可能性。我们将分析新发现的蛋白质复合物在目的地释放货物和失活驱动蛋白-1中的作用。这项工作将为驱动蛋白-1在神经细胞中的功能提供令人兴奋的新见解。这项工作也将增加我们对马达蛋白的调节如何引起细胞中蛋白复合物的协调运输的理解，并将提出人类疾病的治疗靶点。

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.