Assembly and Placement of the Cell Division Ring

描述（由申请人提供）：微管和肌动蛋白之间的相互作用对于细胞中适当的空间组织至关重要。在动物细胞的细胞质分裂过程中，有丝分裂纺锤体的微管定位于细胞分裂平面。微管和肌动蛋白之间的类似相互作用似乎也调节细胞极性和细胞迁移。这些相互作用的分子机制尚不清楚。我们研究了裂糖酵母（Schizosaccharomyces pombe）的空间调控，裂糖酵母是一种杆状细胞，从细胞尖端生长，中间分裂。这项工作的目的是确定细胞分裂和细胞生长的位置在细胞中的位置。我们的初步结果表明，细胞极性和细胞质分裂是由颗粒调节的，这些颗粒移动到细胞尖端或细胞中部，停靠在质膜上，然后诱导肌动蛋白结构的组装（细胞生长的肌动蛋白索或细胞分裂的收缩肌动蛋白环）。在这项资助中，我们建议研究这些关键的运动粒子：它们如何移动到细胞中的特定位置，它们的分子组成是什么，它们的功能是什么？我们的具体目标是：1)确定微管的正端如何在细胞尖端沉积含有细胞极性因子tea1p的颗粒；2)确定tea1p如何在细胞尖端发挥作用，以招募组装肌动蛋白电缆的“极化体”蛋白质复合物；3)确定微管和肌动蛋白如何将含有细胞分裂因子cdc12p的运动颗粒靶向到细胞中间的未来细胞分裂位点。这些研究将阐明微管调控肌动蛋白空间分布的分子机制。由于这些过程中的许多蛋白质是保守的，因此这项工作将与细胞极性和细胞分裂的一般机制直接相关，这对理解发育和人类疾病（如癌症）非常重要。

DESCRIPTION (provided by applicant): Interactions between microtubules and actin are critical for proper spatial organization in cells. During cytokinesis in animal cells, microtubules of the mitotic spindle position the cell division plane. Similar interactions between microtubules and actin also appear to regulate cell polarity and cell migration. The molecular mechanisms for these interactions are unknown. We study spatial regulation in the fission yeast Schizosaccharomyces pombe, a rod-shaped cell that grows from the cell tips and divides in the middle. The goal of this work is to determine how the sites of cell division and cell growth are positioned in the cell. Our preliminary results suggest that cell polarity and cytokinesis are regulated by particles that move to the cell tips or to the cell middle, dock at the plasma membrane, and then function to induce assembly of actin structures (actin cables for cell growth or the contractile actin ring for cytokinesis). In this grant, we propose to study these key motile particles: how do they move to specific locations in the cell, what are their molecular compositions and what are their functions? Our specific aims are: 1) to determine how plus-ends of microtubules deposit a particle containing the cell polarity factor tea1p at the cell tips; 2) to determine how tea1p functions at the cell tip to recruit a "polarisome" protein complex that assembles actin cables; 3) to determine how microtubules and actin target a motile particle containing the cytokinesis factor cdc12p to the future cell division site at the middle of the cell. These studies will elucidate a molecular mechanism for how microtubules regulate the spatial distribution of actin. As many of the proteins in these processes are conserved, this work will be directly relevant to general mechanisms of cell polarity and cell division that will be important for understanding development and human diseases such as cancer.