Assembly and Placement of the Cell Division Ring

描述（由申请人提供）：细胞分裂平面的正确定位对细胞增殖至关重要，并影响细胞分化、组织结构的建立和细胞形态发生等发育过程。对细胞分裂机制的基本认识在癌症生物学和干细胞生物学等人类疾病领域具有广泛的相关性。这项资助的总体目标是确定细胞分裂和细胞极化的基本机制。在我们的研究中，我们使用了一种简单的，遗传上易于处理的模式生物，分裂酵母裂糖酵母。分裂位点定位的一个关键过程是细胞质分裂因子mid1p在覆盖细胞核的内侧皮质区域的定位。在有丝分裂过程中，mid1p将其他细胞分裂因子招募到该位点，以启动基于动作蛋白的收缩环的组装。我们已经发现，不同的细胞成分有助于mid1p定位到这个皮质位置。我们的具体目标集中在表征调节这一过程的新成分：内质网和pom1p激酶的梯度，这是由微管间接建立的。我们的创新方法包括测量活细胞内蛋白质的动态行为和使用微制造室改变细胞形状。这些研究有望在定量理解这一保守的、普遍的过程方面取得重大进展，并阐明构建细胞时使用的全球空间调节的一般概念。

DESCRIPTION (provided by applicant): The proper positioning of the cell division plane is critical for cellular proliferation, and influences developmental processes such as cell differentiation, establishment of tissue architecture, and cell morphogenesis. The basic understanding of mechanisms of cytokinesis has broad relevance to human disease in areas such as cancer biology and stem cell biology. The general goal of this grant is to determine basic, fundamental mechanisms of cytokinesis and cell polarization. For our studies, we use a simple, genetically tractable model organism, the fission yeast Schizosaccharomyces pombe. A key process in division site placement is the localization of a cytokinesis factor mid1p to a medial cortical region overlying the nucleus. During mitosis, mid1p recruits other cytokinesis factors to this site to initiate the assembly of the actin-based contractile ring. We have discovered that diverse cellular components contribute to the localization of mid1p to this cortical location. Our specific aims focus on characterizing new components that regulate this process: the endoplasmic reticulum, and a gradient of the pom1p kinase, which is indirectly set up by microtubules. Our innovative approaches include measuring the dynamic behavior of proteins inside of living cells and altering cell shapes using micro-fabricated chambers. These studies promise to provide a significant advance in the quantitative understanding of this conserved, universal process and elucidate general concepts of global spatial regulation used in building the cell. PUBLIC HEALTH RELEVANCE: The placement of the cell division plane is a fundamental cellular process critical for cellular proliferation and development. Mistakes in cytokinesis are likely to contribute to the development of the cancer cell. These studies on elucidating basic mechanisms using fission yeast as a model organism are highly relevant towards understanding human cell biology and disease.