Mechanisms Regulating Contractile Ring in Fission Yeast

描述(申请人提供)：物理细胞的平等分裂直接影响一代细胞向下一代细胞转移一套完整的染色体。因此，严格规范细胞分裂过程是预防癌症的当务之急。在分裂酵母和人类细胞中，基于肌动球蛋白的收缩环在有丝分裂期间聚集在细胞的内侧区域，并在空间上决定细胞将在哪里物理分离。然而，有助于正确的环形成和功能的分子机制尚不清楚。这个项目的长期目标是阐明一个功能齐全的环所需的监管控制。我们的初步结果表明，在分裂酵母中，类CDC14磷酸酶Clplp与Midlp相互作用，Midlp是正确放置环所需的苯丙素同系物。利用生化分析和分子成像技术，本应用的目的是表征这两个环的成分及其相互作用，以便在分子水平上了解收缩环。人们预计，在简单系统中研究有助于细胞分裂的保守蛋白质和分子机制将加快产生必要的知识，从而显著提高我们对高等生物中细胞分裂的理解。

DESCRIPTION (provided by applicant): Equal division of the physical cell directly influences the transfer of a complete set of chromosomes from one cell generation to the next. Therefore, it is imperative for cancer prevention that the cell division process is strictly regulated. In fission yeast and human cells, an actomyosin based contractile ring assembles at the medial region of the cell during mitosis and spatially dictates where the cell will physically separate. However, the molecular mechanisms that contribute to proper ring formation and function are unclear. The long- term goal of this project is to elucidate the regulatory controls necessary for a fully functional ring. Our preliminary results indicate that in fission yeast the Cdc14-like phosphatase, Clplp, interacts with Midlp, an anillin homolog required for correct ring placement. Utilizing biochemical assays and molecular imaging tech- niques, the objective of this application is to characterize these two ring components and their interaction in order to understand the contractile ring at a molecular level. It is expected that examining conserved proteins and molecular mechanisms that contribute to faithful cell division in simple systems will expedite the generation of knowledge necessary to significantly improve our understanding of cell division in higher organisms.