Effect of Chromokinesins on Spindle Microtubule Dynamics

染色激肽对纺锤体微管动力学的影响

• 批准号: 7157757
• 负责人: Benjamin Houghtaling
• 金额: $ 4.4万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7157757
• 关键词: Xenopus oocyte; cell line; chromosome movement; fluorescence microscopy; kinesin; microtubules; mitotic spindle apparatus; polymerization; postdoctoral investigator; protein structure function; recombinant proteins; site directed mutagenesis

DESCRIPTION (provided by applicant): The faithful segregation of genetic material during cell division is necessary for the development and survival of an organism; errors in this process in humans can result in birth defects and cancer. Essential to the process of cell division is the spindle; a structure comprised of microtubules that associates with chromosomes, enabling the directed movement of genetic material. The spindle can form by two pathways: 1) centrosome dependent, and 2) acentrosomal. Microtubule dynamics are well characterized for the centrosome dependent pathway, but not the acentrosomal pathway; microtubule dynamics in the acentrosomal pathway will be investigated. Motor proteins in the kinesin and dynein family contribute to spindle formation and function. While the contribution of motors such as Eg5, dynein, and Kin I kinesins (MCAK and Kif2a) to microtubule polymerization and transport have been well studied, little is known about the the role of chromokinesins in this process. State of the art microscopy techniques, combined with a powerful in vitro spindle assembly system, will allow studies of spindle dynamics in cells where chromokinesins are perturbed. Quantitative models of spindle formation and organization can then be built.

描述（由申请人提供）：细胞分裂过程中遗传物质的忠实分离是生物体发育和生存所必需的；人类在这一过程中的错误可能导致出生缺陷和癌症。在细胞分裂过程中，纺锤体是必不可少的；由微管组成的结构，与染色体结合，使遗传物质定向运动。纺锤体的形成有两种途径：1)依赖中心体，2)无丝胞体。微管动力学在中心体依赖途径中有很好的特征，但在无丝胞体途径中没有；微管动力学在无丝胞体途径将被研究。运动蛋白和动力蛋白家族中的运动蛋白参与纺锤体的形成和功能。虽然马达如Eg5、动力蛋白和Kin I驱动蛋白（MCAK和Kif2a）对微管聚合和运输的贡献已经得到了很好的研究，但对染色体驱动蛋白在这一过程中的作用知之甚少。最先进的显微镜技术，结合强大的体外纺锤体组装系统，将允许在染色体驱动蛋白受到干扰的细胞中研究纺锤体动力学。然后可以建立主轴形成和组织的定量模型。