细胞极性（即不对称性）是上皮细胞功能的重要特征之一。细胞有丝分裂重要蛋白激酶（如：PLK1）通过调控纺锤体的取向来决定子细胞的极性形成。但是，人们对PLK1激酶通过调控纺锤体的取向与细胞极性形成的分子机制及所涉及的蛋白质网络知之甚少。利用功能蛋白质组学技术与生化鉴定，我们发现并初步解析了PLK1与细胞极性调控蛋白Ezrin及ACAP4的作用机制。我们设想：PLK1通过磷酸化ACAP4与Ezrin，调控细胞有丝分裂期纺锤体的正确取向与子细胞极性的形成。我们拟详尽评估PLK1磷酸化ACAP4及Ezrin的生物化学功能，解析PLK1调控ACAP4-Ezrin复合体在细胞极性形成过程中的动态组装规律，为全面认识有丝分裂退出、上皮细胞极性形成与维系的分子机制奠定基础，并为揭示细胞有丝分裂差错与细胞极性丧失介导的相关病理机制提供启迪。

Polarity, asymmetry, is a unique characteristic of epithelial cells. Mounting evidence suggests that mitotic kinases such as PLK1 govern cellular polarity establishment of daughter cells via specifying the spindle orientation. However, it has remained elusive as to the underlying mechanisms and protein circuitry. Using a combination of mass spectrometric identification and biochemical characterization, we have established the interrelationship between PLK1 and ezrin-ACAP4. In addition, we have pinpointed PLK1-mediated phosphorylation sites on ACAP4 and ezrin. Based on our preliminary work, we hypothesize that PLK1 orchestrates an accurate spindle orientation via regulating a dynamic interactions between actin cortex and microtubule plus-ends via ACAP4-ezrin complex. We plan to evaluate the role of ACAP4 phosphorylation by assessing ACAP4-ARF6 interaction. The functional regulation of phosphorylation of ezrin will be examined by actin co-sedimentation and pyrine assay. The roles of ACAP4-Ezrin complex in mitotic exit, cell polarity establishment and maintenance will be examined. A better understanding of mitotic exit and polarity establishment is of general importance as aberrant mitotic exit and cellular polarity would contribute to pathogeneses of diseases.