Microtubule motors, cytoskeletal organization and cell polarity

项目摘要 这个项目的总体目标是了解微管运动蛋白和动力蛋白是如何组织的 间期细胞中的细胞骨架，结果是驱动细胞极化。我们小组最近发现， 主要的马达蛋白，运动蛋白-1和细胞质动力蛋白，除了移动多种类型的货物 微管有一个新的功能：它们定义了两类微管的分布和动力学行为 间期细胞中的细胞骨架丝、微管和中间丝。我们已经证明，两者 微管和中间细丝由马达蛋白以聚合物的形式运输。这条交通工具 定义细胞骨架的一般组织，并因此定义细胞的极性。人的三种生物学模型 在这一建议中研究的极化是：(I)果蝇神经元，其中微管运动由kinesin-1 驱动轴突和树突的初始伸展，皮质动力蛋白将轴突微管均匀地分类成 极化排列；(Ii)果蝇卵母细胞，其中Kinesin-1运输微管驱动 对胚胎发育至关重要的极性决定因素的细胞质定位和细胞质动力蛋白 在哺乳细胞内和从哺育细胞到卵母细胞的微管运输和(Iii)中间体的运输 哺乳动物细胞中沿着微管的细丝，这对细胞的定向迁移很重要。

Project Summary The overall goal of this project is to understand how microtubule motors kinesin and dynein organize cytoskeleton in interphase cells and, as a result, drive cell polarization. Our group recently discovered that major motor proteins, kinesin-1 and cytoplasmic dyneins, in addition to moving many types of cargoes along microtubules, have a new function: they define the distribution and dynamic behavior of two classes of cytoskeletal filaments, microtubules and intermediate filaments in interphase cells. We have shown that both microtubules and intermediate filaments are being transported as polymers by motor proteins. This transport defines general organization of the cytoskeleton, and, as a result, cell polarity. Three biological models of polarization studied in this proposal are: (i) Drosophila neurons, where movement of microtubules by kinesin-1 drives initial extension of axons and dendrites, and cortical dynein sorts axonal microtubules into uniformly polarized arrays; (ii) Drosophila oocytes, where transport of microtubules by kinesin-1 drives rotation of cytoplasm for localization of polarity determinants critical for the developing embryo, and cytoplasmic dynein transports microtubules in nurse cells and from nurse cells to the oocyte and (iii) transport of intermediate filaments along microtubules in mammalian cells, which is important for directed cell migration.