DDA3 RECRUITS MICROTUBULE DEPOLYMERASE KIF2A TO SPINDLE POLES AND CONTROLS SPIND

DDA3 将微管解聚酶 KIF2A 招募到主轴并控制旋转

• 批准号: 7723660
• 负责人: GUOWEI FANG
• 金额: $ 0.08万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7723660
• 关键词: Anaphase; Chromosome Segregation; Chromosomes; Class; Computer Retrieval of Information on Scientific Projects Database; Frequencies; Funding; Grant; Institution; Kinetochores; Metaphase; Microtubule Polymerization; Microtubules; Mitosis; Mitotic; Mitotic spindle; Phenocopy; Proteins; Rate; Recruitment Activity; Research; Research Personnel; Resources; Sister; Source; United States National Institutes of Health; driving force; functional genomics; segregation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Dynamic turnover of the spindle is a driving force for chromosome congression and segregation in mitosis. Through a functional genomic analysis, we identify DDA3 as a previously unknown regulator of spindle dynamics that is essential for mitotic progression. DDA3 depletion results in a high frequency of unaligned chromosomes, a substantial reduction in tension across sister kinetochores at metaphase, and a decrease in the velocity of chromosome segregation at anaphase. DDA3 associates with the mitotic spindle and controls microtubule (MT) dynamics. Mechanistically, DDA3 interacts with the MT depolymerase Kif2a in an MT-dependent manner and recruits Kif2a to the mitotic spindle and spindle poles. Depletion of DDA3 increases the steady-state levels of spindle MTs by reducing the turnover rate of the mitotic spindle and by increasing the rate of MT polymerization, which phenocopies the effects of partial knockdown of Kif2a. Thus, DDA3 represents a new class of MT-destabilizing protein that controls spindle dynamics and mitotic progression by regulating MT depolymerases

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 主轴的动态周转率是染色体会议和有丝分裂隔离的推动力。通过功能性基因组分析，我们将DDA3识别为先前未知的纺锤体动力学调节剂，这对于有丝分裂进展至关重要。 DDA3耗竭会导致高染色体的高频率，在中期姊妹动物学上的张力大大降低，并降低了后期染色体分离的速度。 DDA3与有丝分裂纺锤体并控制微管（MT）动力学相关。从机械上讲，DDA3以MT依赖性方式与MT去聚合酶KIF2A相互作用，并将KIF2A募集到有丝分裂的纺锤体和主轴杆上。 DDA3的耗竭通过降低有丝分裂主轴的周转速率和增加MT聚合速率来增加纺锤体MT的稳态水平，从而使MT聚合的速率降低了KIF2A的部分敲低的效果。因此，DDA3代表了一类新的MT Destabilizatization蛋白，该蛋白通过调节MT解放酶来控制纺锤体动力学和有丝分裂进展