Characterization of Novel Importin-Beta Targets in Mitotic Spindle Assembly

有丝分裂纺锤体组装中新型导入β靶标的表征

• 批准号: 0344723
• 负责人: Christiane Wiese
• 金额: --
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2007-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0344723&HistoricalAwards=false
• 关键词: Characterization; Novel; Importin; Beta; Targets

Temporal and spatial control of microtubule nucleation and organization are essential for several fundamental cellular processes, including cellular shape changes, intracellular transport, cell motility, cytoplasmic partitioning during embryonic development, and the separation of chromosomes during cell division. Most eukaryotic cells contain an elaborate macromolecular machine, the mitotic spindle, which ensures that a complete set of chromosomes is distributed to each subcell during cell division. Mitotic spindle assembly is a highly orchestrated process that is tightly regulated to avoid mistakes in chromosome segregation that could lead to developmental defects, cell death, or genomic instability. Using the Xenopus model system, the PI has identified importin-b and an interacting protein, maskin, as key proteins in the regulation of mitotic spindle assembly. This new project continues the PI's research on understanding the molecular mechanism of how importin-b and maskin regulate mitotic spindle assembly. The specific questions that will be addressed include: What is the effect on spindle assembly of altering the levels of maskin? What are the maskin interacting partner(s)? What is the effect of maskin on microtubules in vitro? Is there a link between maskin's role in spindle assembly and its role in translational regulation? How is maskin regulated? What is the role of importin-b in the regulation of maskin? Results from this project will further the understanding of the role of maskin and other mitotic spindle assembly factors in the spatial and temporal regulation of microtubule assembly and organization during early development in Xenopus, which may also shed light on the function of other members of this family of proteins. The results will also further the understanding of how importin-b regulates spindle assembly and will provide new insights into the role that importin-b and maskin and/or their human homologs play more generally in the life of a cell or an organism. The project will provide research training at three levels: undergraduate, graduate and postdoctoral.

微管成核和组织的时间和空间控制对于几个基本的细胞过程是必不可少的，包括细胞形状变化、细胞内运输、细胞运动、胚胎发育期间的细胞质分配以及细胞分裂期间染色体的分离。大多数真核细胞都含有一个复杂的大分子机器，即有丝分裂纺锤体，它确保在细胞分裂过程中将一套完整的染色体分配给每个亚细胞。有丝分裂纺锤体组装是一个高度协调的过程，其被严格调控以避免可能导致发育缺陷、细胞死亡或基因组不稳定的染色体分离错误。使用非洲爪蟾模型系统，PI已确定importin-b和相互作用的蛋白质，maskin，作为有丝分裂纺锤体组装调控的关键蛋白质。这个新项目继续PI的研究，了解importin-b和maskin如何调节有丝分裂纺锤体组装的分子机制。将解决的具体问题包括：改变掩蔽水平对主轴组件有何影响？什么是掩蔽相互作用伙伴？面膜在体外对微管有什么影响？maskin在纺锤体组装中的作用与其在翻译调控中的作用之间是否存在联系？口罩是如何规定的？importin-b在调节maskin中的作用是什么？从这个项目的结果将进一步了解面具和其他有丝分裂纺锤体组装因子在空间和时间调控微管组装和组织在非洲爪蟾早期发育过程中的作用，这也可能揭示这个蛋白质家族的其他成员的功能。这些结果也将进一步了解importin-b如何调节纺锤体组装，并将为importin-b和maskin和/或它们的人类同源物在细胞或生物体的生命中更普遍地发挥作用提供新的见解。该项目将提供三个层次的研究培训：本科生、研究生和博士后。