Spatial Organization of Cytoskeletal Asymmetry

细胞骨架不对称的空间组织

• 批准号: 8997508
• 负责人: Irina Kaverina
• 金额: $ 41.44万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8997508
• 关键词: A-Microtubule; AKAP9 gene; Accounting; Actins; Address; Area; Behavior; Binding Proteins; Cell Cycle; Cell Nucleus; Cell division; Cells; Cellular biology; Centrosome; Cytoskeletal Modeling; Cytoskeleton; Data; Dynein ATPase; Ensure; Event; Face; Funding; Goals; Golgi Apparatus; Health; Homeostasis; Interphase; Laboratories; Life Cycle Stages; Location; Maintenance; Membrane; Microtubules; Minus End of the Microtubule; Mitotic; Modeling; Molecular; Molecular Motors; Motor; Nature; Nuclear Envelope; Organelles; Polymers; Population; Positioning Attribute; Process; Property; Prophase; Publishing; Radial; Recycling; Role; Shapes; Side; Site; Specificity; Staging; Testing; Ursidae Family; Vesicle; base; cell motility; daughter cell; directional cell; late endosome; novel; polarized cell; research study; trafficking; trans-Golgi Network

DESCRIPTION (provided by applicant): Microtubule (MT) properties vary within seemingly uniform MT network, and MTs with similar properties comprise functionally specialized subsets. In the current funding period, we have characterized a distinct MT subset that nucleates at the Golgi membrane (Golgi-derived MTs). In contrast to the radially organized centrosomal MTs, Golgi-derived MT array is intrinsically asymmetric and is essential for polarity of motile cells. Our previous and preliminary data indicate that Golgi-derived MTs bear unique functions. Being closely associated with the Golgi membrane, these MTs are indispensable for Golgi complex assembly, maintenance and positioning. Despite the obvious essential nature of the maintenance and reorganization of the Golgi in the life cycle and basic behavior of all cells, there is a poor understanding of the intracellular architectural mechanisms that orchestrate its dynamic, temporally regulated functions. Major gaps addressed by our study include: how vesicles are tracked to/from the Golgi, how stack alignment is ensured during Golgi complex assembly, and how they are timely relocated at mitotic onset. Our preliminary and published data indicate that Golgi-derived MTs act as the architectural basis of these precisely coordinated processes. We hypothesize that distinct location of Golgi-derived MTs with their minus ends at the Golgi membrane and their specific association with a MT-binding protein CLASP, which differentially regulates distinct molecular motors, underlies functional specificity of this MT subset. The goal of this proposal is to determine the spatial and molecular mechanisms underlying the unique functions of Golgi-derived MTs. The proposal thus targets a high- impact, fundamental area of mechanistic cell biology. Our specific aims are: 1. Test whether vesicle delivery driven by Golgi-derived MTs is critical for Golgi homeostasis 2. Determine whether Golgi repositioning prior to cell division is accomplished by Golgi-derived MTs 3. Determine the mechanism whereby Golgi-derived MTs support efficient Golgi stack fusion

描述（由申请人提供）：微管（MT）的性质在看似统一的MT网络中有所不同，具有相似性质的MT包括功能专门的子集。在目前的资助期内，我们已经描述了在高尔基膜上成核的独特MT亚群（高尔基衍生MT）。与放射状组织的中心体MT相反，高尔基衍生的MT阵列本质上是不对称的，对于运动细胞的极性是必不可少的。我们之前和初步的数据表明高尔基衍生的mt具有独特的功能。这些mt与高尔基膜密切相关，对高尔基复合体的组装、维护和定位是必不可少的。尽管在所有细胞的生命周期和基本行为中，高尔基体的维持和重组具有明显的本质，但对协调其动态、临时调节功能的细胞内结构机制的理解却很差。我们的研究解决的主要空白包括：如何跟踪囊泡进出高尔基体，如何在高尔基体组装期间确保堆栈对齐，以及它们如何在有丝分裂开始时及时重新定位。我们的初步和发表的数据表明，高尔基衍生的mt作为这些精确协调过程的架构基础。我们假设，高尔基衍生MT的独特位置及其负端在高尔基膜上，以及它们与MT结合蛋白CLASP的特异性关联，该蛋白对不同的分子马达进行差异调节，是该MT亚群功能特异性的基础。本提案的目标是确定高尔基衍生mt的独特功能背后的空间和分子机制。因此，该提案针对机械细胞生物学的一个高影响力的基础领域。我们的具体目标是：1。测试由高尔基衍生mt驱动的囊泡递送是否对高尔基体内平衡至关重要2。确定细胞分裂前的高尔基重定位是否由高尔基衍生的mt3完成。确定高尔基衍生mt支持高效高尔基堆栈融合的机制