Cytokinesis and the Cytoskeleton in C. elegans Embryos

线虫胚胎中的细胞分裂和细胞骨架

• 批准号: 8002526
• 负责人: BRUCE A BOWERMAN
• 金额: $ 17.7万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-14 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8002526
• 关键词: Adaptor Signaling Protein; Caenorhabditis elegans; Cell Cycle Progression; Cell division; Collaborations; Collection; Complex; Cytokinesis; Cytoskeleton; Defect; Embryo; Failure; Family; Fertilization; Genes; Genetic Screening; Investigation; Malignant Neoplasms; Mediating; Meiosis; Microfilaments; Microtubules; Mitosis; Mitotic spindle; Molecular Genetics; Neurodegenerative Disorders; Processed Genes; RNA Interference; Regulation; Research; Saccharomycetales; Specificity; Switzerland; Ubiquitin; Ubiquitin-mediated Proteolysis Pathway; base; chromokinesin; human disease; improved; insight; katanin; member; mutant; novel; scaffold; ubiquitin-protein ligase

DESCRIPTION (provided by applicant): Progress on our specific aims over the past four years has led to our discovery of a novel and conserved class of ubiquitin E3 ligases that targets a subunit of the microtubule-severing complex called katanin for ubiquitin-mediated proteolytic degradation, shortly after the completion of meiosis. Katanin is required for meiosis; its subsequent degradation is required for the proper assembly of mitotic spindles, and for the regulation of cortical microfilament contractility during cytokinesis. Thus in addition to influencing regulators of cell cycle progression, we have shown that ubiquitin-mediated proteolysis also influences the cell division machinery itself. Importantly, the E3 ligase we discovered is the founding member of a new class of Cullin- based E3 ligases, composed of a Cullin3 scaffold and one of a large and conserved family of novel adaptor proteins. This finding greatly extends our understanding of the full range of ubiquitin E3 target specificity, and we also have provided new insights into the regulation of E3 ligases. Finally, from extensive screens for conditional mutants with cell division defects, we have identified (i) a chromokinesin, and three additional mutants, that influence central spindle assembly or stability, and the completion of cytokinesis, and (ii) a large collection of meiosis-defective mutants. Our new aims seek to improve our understanding of cytokinesis and meiosis through a molecular genetic investigation of these new mutants. We also will continue our efforts to identify factors that influence E3 ligase function and katanin degradation, in an ongoing collaboration with Dr. Matthias Peter at the ETH in Zurich, Switzerland. The processes and genes we propose to investigate are relevant to important human diseases, including cancer and neurodegenerative disease.

描述（由申请人提供）：过去四年来我们的具体目标进展，导致我们发现了一种新颖而保守的泛素E3连接酶，该连接酶的靶向微管 - 细分 - 分布katanin的亚基，称为katanin，用于泛素蛋白介导的蛋白水解介导的蛋白水解介导在减数分裂完成后不久。 Katanin是减数分裂所必需的；其随后的降解是正确组装有丝分裂纺锤体以及在细胞球运动过程中皮质微丝收缩性的调节所必需的。因此，除了影响细胞周期进程的调节剂外，我们还表明，泛素介导的蛋白水解还会影响细胞分裂机械本身。重要的是，我们发现的E3连接酶是由Cullin3支架组成的新型Cullin-E3连接酶的创始成员，也是一个大型且保守的新型适配器蛋白家族之一。这一发现极大地扩展了我们对泛素E3目标特异性的全部理解，我们还为E3连接酶的调节提供了新的见解。最后，从具有细胞分裂缺陷的有条件突变体的庞大筛选中，我们已经确定了（i）染色体动物蛋白和三个影响中央主轴组件或稳定性的其他突变体，以及细胞因子的完成，以及（ii）大量的减毒症。 - 缺陷突变体。我们的新目标旨在通过对这些新突变体的分子遗传研究来提高我们对细胞因子和减数分裂的理解。我们还将继续努力确定影响E3连接酶功能和Katanin降解的因素，并与瑞士苏黎世ETH的Matthias Peter博士进行了持续的合作。我们建议进行研究的过程和基因与包括癌症和神经退行性疾病在内的重要人类疾病有关。

项目成果

Conditional dominant mutations in the Caenorhabditis elegans gene act-2 identify cytoplasmic and muscle roles for a redundant actin isoform.

秀丽隐杆线虫基因 act-2 的条件显性突变可识别冗余肌动蛋白亚型的细胞质和肌肉作用。

• DOI: 10.1091/mbc.e05-09-0886
• 发表时间: 2006
• 期刊: Molecular biology of the cell
• 影响因子: 3.3
• 作者: Willis,JohnH;Munro,Edwin;Lyczak,Rebecca;Bowerman,Bruce
• 通讯作者: Bowerman,Bruce

Metaphase to anaphase (mat) transition-defective mutants in Caenorhabditis elegans.

• DOI: 10.1083/jcb.151.7.1469
• 发表时间: 2000-12-25
• 期刊: The Journal of cell biology
• 作者: Golden A;Sadler PL;Wallenfang MR;Schumacher JM;Hamill DR;Bates G;Bowerman B;Seydoux G;Shakes DC
• 通讯作者: Shakes DC