Regulation of cytokinesis by cell polarity signaling

细胞极性将细胞骨架丝定向到空间地标，指导局部细胞生长。 蛋白激酶通过将空间信号转化为对细胞极性的调节， 包括肌动蛋白和肌球蛋白的细胞骨架蛋白。在细胞分裂时，肌动球蛋白 急剧重组成一个细胞动力学环，收缩分离分裂细胞。我们 假设细胞极性激酶直接作用于收缩性肌动球蛋白环（CAR）， 促进其在胞质分裂中的组装、组织和功能。在这个模型中，细胞极性 信号蛋白在胞质分裂中调节CAR，类似于它们在其他肌动球蛋白上的作用 极化增长的结构。我们利用裂殖酵母S. pombe作为一个模型系统，因为它提供了一个定义良好的零件清单和一个实验主机， 优势我们的初步数据表明，三个保守的细胞极性蛋白激酶Pak 1， Kin 1和Pom 1-直接磷酸化CAR蛋白并调节CAR中的特定步骤 在细胞分裂过程中的组装和收缩。此外，磷酸酶PP 2A的调节剂 在胞质分裂过程中保持CAR锚定在正确的位置。我们建议 了解这些保守的蛋白激酶的分子机制， 磷酸酶作用于CAR以促进细胞分裂。该补助金的具体目标是：（1） 确定Pak 1在细胞分裂过程中如何调节细胞骨架，（2）测试假设， Pom 1、Kin 1和Pak 1代表胞质分裂蛋白的顺序调控输入，以及（3） 研究PP 2A磷酸酶的调节如何定位CAR。成功完成 这些目标将定义一个防止细胞分裂缺陷的信号系统， 两个基本细胞过程之间的先前未知的联系：细胞极性和 胞质分裂

Cell polarity orients cytoskeletal filaments toward spatial landmarks, directing local cell growth. Protein kinases play key roles in cell polarity by translating spatial signals into regulation of cytoskeletal proteins including actin and myosin. At cell division, the actomyosin machinery dramatically reorganizes into a cytokinetic ring that constricts to separate the dividing cells. We hypothesize that cell polarity kinases act directly on the contractile actomyosin ring (CAR) to promote its assembly, organization, and function in cytokinesis. In this model, cell polarity signaling proteins regulate the CAR in cytokinesis analogous to their roles on other actomyosin structures in polarized growth. We study cell polarity and cytokinesis using the fission yeast S. pombe as a model system because it offers a well-defined parts list and a host of experimental advantages. Our preliminary data show that three conserved cell polarity protein kinases—Pak1, Kin1, and Pom1—directly phosphorylate CAR proteins and regulate specific steps in CAR assembly and constriction during cell division. In addition, regulators of the phosphatase PP2A are required to keep the CAR anchored in the correct place during cytokinesis. We propose to understand the molecular mechanisms by which these conserved protein kinases and phosphatases act on the CAR to promote cell division. The specific aims of this grant are to: (1) determine how Pak1 regulates the cytoskeleton during cell division, (2) test the hypothesis that Pom1, Kin1, and Pak1 represent sequential regulatory inputs for cytokinesis proteins, and (3) investigate how regulation of PP2A phosphatase positions the CAR. Successful completion of these goals will define a signaling system that prevents defects in cell division, and will identify previously unknown connections between two fundamental cellular processes: cell polarity and cytokinesis.