CELL POLARITY AND SPINDLE POSITION

有丝分裂纺锤体正确地定位在分裂区内 细胞是S.啤酒。 纺锤体定位对于许多生物体中的细胞分裂是必不可少的，并且是一种重要的生物学机制。 产生特异性非对称细胞分裂的关键调节步骤 细胞发育过程中。主轴定位被认为是由 星形微管与不对称定位因子的相互作用 在细胞皮层。纺锤体定位的特定分子基础不是 已知，但在一些生物体中，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，酵母细胞延迟在 胞质分裂的起始。这种细胞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 酵母有一种机制，可以“感知”纺锤体位置的缺陷并纠正它们 (the胞质分裂检查点）。该提案的目的是定义 纺锤体定位的分子机制和表征信号传导 将纺锤体位置与其他细胞周期事件联系起来的过程。最近的工作 该实验室已确定了该系统的关键组件，并启动了 其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.