The Mechanism and Regulation of Cytokinesis in Yeast

酵母细胞分裂的机制和调控

• 批准号: 6781734
• 负责人: RONG LI
• 金额: $ 29.66万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6781734
• 关键词: Saccharomyces cerevisiae; actins; biological transport; cell cycle; cell cycle proteins; cell growth regulation; cytogenetics; exocytosis; fungal genetics; fungal proteins; genetic techniques; immunocytochemistry; membrane activity; microorganism reproduction; myosins; protein localization; video microscopy

DESCRIPTION (provided by applicant): Mitotic cell division is fundamental to the growth and development of eukaryotic organisms. The final crucial step in cell division that results in cytoplasmic separation of progeny cells is a process known as cytokinesis. Cytokinesis in animal cells and yeast require membrane constriction driven by an actomyosin-based contractile ring and targeted membrane insertion at the site of cell cleavage. Successful cell division depends on spatial and temporal coordination of these cytokinetic events with chromosome segregation. We have been using the budding yeast Saccharomyces cerevisiae as the model to study the intricate structural and regulatory steps required for cytokinesis. We have shown that assembly of the contractile ring in budding yeast occurs in two temporally separate stages during which myosin-II and actin filaments assemble into a ring around the bud neck connecting the mother and daughter cells. Contraction of this ring at the onset of cytokinesis is regulated by the mitotic exit network. The exocytic pathway is also directed to the bud neck around the time of cytokinesis, and preliminary results suggest that this event is required for cytokinesis. Three specific aims are proposed. First, we will further investigate how myosin-II is recruited to the site of cell division at the G1/S transition and how actin filaments are assembled in the contractile ring during anaphase. Second, we will try to identify the molecular target(s) of the mitotic exit network in triggering the onset of cytokinesis. Finally, we will investigate how the exocytic pathway is directed toward cell division site during mitosis. The experimental approach involves a combination of genetic, biochemical, and microscopy imaging techniques. Because the cell cycle regulatory pathways and the structural components of the cell division site are similar between yeast and animal cells, our study is likely to provide valuable insights into the conserved mechanisms that control cytokinesis in eukaryotes.

描述（由申请人提供）：有丝分裂细胞分裂是真核生物的生长和发育至关重要的。细胞分裂的最终关键步骤导致后代细胞的细胞质分离是一种称为细胞因子的过程。动物细胞和酵母中的细胞因子需要膜收缩环和细胞裂解部位的靶向膜插入驱动的膜收缩。成功的细胞分裂取决于与染色体分离的这些细胞动力学事件的空间和时间协调。我们一直在使用酿酒酵母的萌芽酵母菌作为研究细胞因子所需的复杂结构和调节步骤的模型。我们已经表明，收缩酵母中收缩环的组装发生在两个时间分开的阶段，在此期间，肌球蛋白-II和肌动蛋白细丝将连接母细胞的芽颈周围的环组装成一个环。在细胞因子开始时，该环的收缩受丝分裂出口网络调节。胞外途径也针对细胞动力学时期的芽颈，初步结果表明该事件是细胞因子所必需的。 提出了三个具体目标。首先，我们将进一步研究如何在G1/s过渡时将肌球蛋白II招募到细胞分裂部位，以及如何在后期期间将肌动蛋白丝组装在收缩环中。其次，我们将尝试确定有丝分裂出口网络的分子靶标，以触发细胞因子的发作。最后，我们将研究有丝分裂期间如何针对细胞分裂位点的外囊肿途径。实验方法涉及遗传，生化和显微镜成像技术的结合。由于细胞周期调节途径和细胞分裂位点的结构成分在酵母菌和动物细胞之间相似，因此我们的研究可能会提供对控制真核生物中细胞因子的保守机制的宝贵见解。