School of Biological Sciences, College of Science, Nanyang Technological University, 637551 Singapore.
J Cell Sci. 2014 Feb 15;127(Pt 4):727-39. doi: 10.1242/jcs.126482. Epub 2013 Dec 11.
The kinesin motors are important in the regulation of cellular functions such as protein trafficking, spindle organization and centrosome separation. In this study, we have identified POPX2, a serine-threonine phosphatase, as an interacting partner of the KAP3 subunit of the kinesin-2 motor. The kinesin-2 motor is a heterotrimeric complex composed of KIF3A, KIF3B motor subunits and KAP3, the non-motor subunit, which binds the cargo. Here we report that the phosphatase POPX2 is a negative regulator of the trafficking of N-cadherin and other cargoes; consequently, it markedly influences cell-cell adhesion. POPX2 affects trafficking by determining the phosphorylation status of KIF3A at serine 690. This is consistent with the observation that the KIF3A-S690A mutant is defective in cargo trafficking. Our studies also implicate CaMKII as the kinase that phosphorylates KIF3A at serine 690. These results strongly suggest that POPX2 and CaMKII are a phosphatase-kinase pair that regulates kinesin-mediated transport and cell-cell adhesion.
驱动蛋白是细胞功能调节中的重要分子，例如蛋白质运输、纺锤体组织和中心体分离。在本研究中，我们鉴定了丝氨酸-苏氨酸磷酸酶 POPX2 是驱动蛋白-2 （kinesin-2） 马达的 KAP3 亚基的相互作用伙伴。驱动蛋白-2 是一种由 KIF3A、KIF3B 运动亚基和 KAP3（非运动亚基，结合货物）组成的异三聚体复合物。在这里，我们报告称磷酸酶 POPX2 是 N-钙粘蛋白和其他货物运输的负调节剂；因此，它显著影响细胞-细胞黏附。POPX2 通过确定丝氨酸 690 处 KIF3A 的磷酸化状态来影响运输。这与 KIF3A-S690A 突变体在货物运输中缺陷的观察结果一致。我们的研究还表明 CaMKII 是磷酸化 KIF3A 丝氨酸 690 的激酶。这些结果强烈表明，POPX2 和 CaMKII 是调节驱动蛋白介导的运输和细胞-细胞黏附的磷酸酶-激酶对。
