Microtubule Organization and Nuclear Positioning

微管组织和核定位

• 批准号: 8215710
• 负责人: Fred Chang
• 金额: $ 34.34万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8215710
• 关键词: Actins; Animal Model; Behavior; Binding; Binding Proteins; Cell Nucleus; Cell Shape; Cell division; Cell physiology; Cells; Chromosome Segregation; Collection; Cytoskeleton; Elements; Event; Exhibits; Filament; Fission Yeast; Genetic; Goals; Grant; Growth; In Vitro; Interphase; Kinetochores; Knowledge; Link; Location; Malignant Neoplasms; Microfilaments; Microtubule Bundle; Microtubule-Associated Proteins; Microtubules; Mitosis; Mitotic spindle; Modeling; Molecular; Nuclear; Play; Plus End of the Microtubule; Positioning Attribute; Process; Regulation; Role; Site; Structure; Testing; Tubulin; Work; cell determination; cell motility; human disease; migration; prevent; public health relevance

DESCRIPTION (provided by applicant): Microtubules are cytoskeletal elements responsible for the spatial organization of cells. They carry out critical cellular processes such as chromosome segregation, cell polarization and cell migration. The dynamic behaviors of MT plus ends - their growth, shrinkage, targeting and attachment -- are modulated by a bevy of MT-associated factors. Here, we study the molecular mechanisms that regulate the MT cytoskeleton, using the fission yeast Schizosaccharomyces pombe as a model organism. Our studies focus on elucidating the mechanisms that regulate the transitions between MT growth and shrinkage, namely MT rescue and catastrophe. Our aims are: 1) to characterize CLASP, a candidate MT rescue factor that stabilizes MTs within the mitotic spindle and interphase MT bundles; 2) to determine why MT catastrophe events occur at specific cortical sites at cell tips; 3) to investigate possible roles of actin in the nucleus, focusing on its effect on chromosome segregation during mitosis. PUBLIC HEALTH RELEVANCE: Microtubules are dynamic filaments responsible for cell division and determination of cell shape and function. In this proposal we will determine how the growth and shrinkage of microtubules are regulated. These studies will provide greater understanding of how mitotic spindles work and will be relevant for human diseases such as cancer.

描述（由申请人提供）：微管是负责细胞空间组织的细胞骨架元件。它们进行关键的细胞过程，如染色体分离，细胞极化和细胞迁移。MT+末端的生长、收缩、靶向和附着等动态行为受到一系列MT相关因子的调控。在这里，我们研究的分子机制，调节MT细胞骨架，使用裂殖酵母粟酒裂殖酵母作为模式生物。我们的研究重点是阐明调节MT生长和收缩之间的转换的机制，即MT拯救和灾难。我们的目标是：1）表征CLASP，一种候选MT拯救因子，其稳定有丝分裂纺锤体和间期MT束内的MT; 2）确定为什么MT灾难事件发生在细胞尖端的特定皮质位点; 3）研究肌动蛋白在细胞核中的可能作用，重点关注其在有丝分裂期间对染色体分离的影响。 公共卫生相关性：微管是负责细胞分裂和决定细胞形状和功能的动态细丝。在这个提议中，我们将确定微管的生长和收缩是如何调节的。这些研究将为有丝分裂纺锤体的工作方式提供更多的了解，并将与人类疾病如癌症有关。

项目成果

CLASP promotes microtubule rescue by recruiting tubulin dimers to the microtubule.

• DOI: 10.1016/j.devcel.2010.07.016
• 发表时间: 2010-08-17
• 期刊: DEVELOPMENTAL CELL
• 影响因子: 11.8
• 作者: Al-Bassam, Jawdat;Kim, Hwajin;Brouhard, Gary;van Oijen, Antoine;Harrison, Stephen C.;Chang, Fred
• 通讯作者: Chang, Fred

The XMAP215 Ortholog Alp14 Promotes Microtubule Nucleation in Fission Yeast.

• DOI: 10.1016/j.cub.2018.04.008
• 发表时间: 2018-06-04
• 期刊: Current biology : CB
• 作者: Flor-Parra I;Iglesias-Romero AB;Chang F
• 通讯作者: Chang F