The Mechanism of Spindle Assembly and Chromosome Alignment

纺锤体组装和染色体排列的机制

• 批准号: 10246849
• 负责人: Yixian Zheng
• 金额: $ 35.54万
• 依托单位: CARNEGIE INSTITUTION OF WASHINGTON, D.C.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10246849
• 关键词: Address; Area; Attention; Binding; Binding Sites; Biochemical; Biological; Biological Assay; Biophysics; Bundling; Cell division; Cells; Chromosome Segregation; Chromosomes; Complex; Diffusion; Disease; Ensure; Funding; Hydrophobicity; In Vitro; Kinetochores; Liquid substance; Mediating; Microtubules; Mitosis; Molecular; Morphogenesis; Phase; Phase Transition; Phosphotransferases; Proteins; Proteome; Publications; Publishing; Reporting; Role; Signaling Molecule; Structure; Testing; Tubulin; Work; base; biophysical analysis; insight; novel; therapeutic target

ABSTRACT Through analyzing the spindle matrix proteome, which we defined in our previous funding periods, we have made a number of exciting observations. Most importantly we have demonstrated that the spindle matrix protein, BuGZ, undergoes oligomerization via phase transition or coacervation to form liquid droplets in vitro mediated in part by the hydrophobic residues found in the intrinsically disorder region of BuGZ. The coacervation activity of BuGZ is essential for assembly of the spindle and its matrix. BuGZ coacervation in vitro as pure protein or in the spindle matrix concentrates tubulin and promotes MT assembly and bundling. Our published and unpublished findings suggest that the interaction and/or coacervation of BuGZ and another spindle assembly factor, TPX2, promotes spindle assembly. Here we propose to use biophysical, biochemical, and cell biological approaches to dissect the molecular mechanism by which these spindle assembly factors synergize to regulate Aurora A activation, microtubule assembly, and kinetochore-microtubule interactions in mitosis.

摘要