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于细胞增殖至关重要，并影响发育过程，如细胞分化、组织结构的建立和细胞形态发生。对胞质分裂机制的基本理解与癌症生物学和干细胞生物学等领域的人类疾病具有广泛的相关性。该基金的总体目标是确定胞质分裂和细胞极化的基本机制。在我们的研究中，我们使用一种简单的，遗传上易于处理的模式生物，裂殖酵母粟酒裂殖酵母。分裂部位定位的一个关键过程是胞质分裂因子mid1p定位于覆盖核的内侧皮质区域。在有丝分裂过程中，mid1p招募其他胞质分裂因子到这个位点，启动肌动蛋白收缩环的组装。我们已经发现，不同的细胞成分有助于mid1p的本地化到这个皮质位置。我们的具体目标集中在表征调节这一过程的新组分：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，以及使用微制造腔室改变细胞形状。这些研究有望提供一个显着的进步，在定量了解这个保守的，普遍的过程，并阐明一般概念的全球空间调控用于建设细胞。 公共卫生相关性：细胞分裂平面的放置是细胞增殖和发育的关键的基本细胞过程。胞质分裂的错误可能会促进癌细胞的发展。这些以裂殖酵母为模式生物阐明基本机制的研究对理解人类细胞生物学和疾病具有高度相关性。

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.