CELL POLARITY AND SPINDLE POSITION

有丝分裂纺锤体在分裂中的位置正确 细胞是酿酒酵母有丝分裂的一个关键但知之甚少的方面。 纺锤体定位在许多生物体的细胞分裂中是必不可少的，是一种 关键调控步骤为产生特定的不对称细胞分裂 发育过程中的细胞类型。主轴定位被认为是由 星体微管与非对称定域因子的相互作用 在细胞皮质。主轴定位的特定分子基础不是 已知，但在几个生物体中，它涉及肌动蛋白和 微管蛋白细胞骨架。当纺锤体定位失败时，酵母细胞在 胞质分裂的启动。该单元周期延迟具有以下特征 检查点机制，因为它可以被特定的突变绕过。因此， 酵母具有“感知”纺锤体位置缺陷并纠正它们的机制 (细胞质分裂检查点)。这项提案的目标是定义 纺锤体定位的分子机制及其信号转导特征 将纺锤体位置与其他细胞周期事件联系起来的过程。近期工作 该实验室已确定了该系统的关键组件并启动了 它们的生物化学和体内功能的表征。因为 主轴定位在开发中的核心作用，这项工作可能会影响 了解遗传性和获得性发育性疾病。

The mitotic spindle is correctly positioned within the dividing cell is a critical but poorly understood aspect of mitosis in S. cerevisiae. Spindle positioning is essential for cell division in many organisms and is a key regulated step for the generation of asymmetric cell divisions of specific cell types during development. Spindle positioning is thought to be mediated by interactions between astral microtubules and asymmetrically localized factors at the cell cortex. The specific molecular basis for spindle positioning is not known, but in several organisms it involves interactions between the actin and tubulin cytoskeletons. When spindle positioning fails, yeast cells delay in the initiation of cytokinesis. This cell cycle delay has the characteristics of a checkpoint mechanism because it can be bypassed by specific mutations. Thus yeast has mechanisms to "sense" defects in spindle position and correct them (the cytokinesis checkpoint). The goal of this proposal is to define the molecular mechanism of spindle positioning and characterize the signaling processes that link spindle position to other cell cycle events. Recent work form this laboratory has identified key components of this system and initiated the characterization of their biochemical and in vivo functions. Because of the central role of spindle positioning in development, this work may impact on the understanding of inherited and acquired developmental diseases.