Department of Biotechnology, Graduate School of Engineering, Osaka University, GSE Common East 7 F, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Acta Histochem Cytochem. 2011 Dec 28;44(6):247-58. doi: 10.1267/ahc.11033. Epub 2011 Oct 22.
ASURA (PHB2) knockdown has been known to cause premature loss of sister chromatid cohesion, and disrupt the localization of several outer plate proteins to the kinetochore. As a result, cells are arrested at mitotic phase and chromosomes fail to congress to the metaphase plate. In this study, we further clarified the mechanism underlying ASURA function on chromosome congression. Interestingly, ASURA is not specifically localized at the kinetochore during mitotic phase, unlike other kinetochore proteins which construct the kinetochore. Electron microscopy (EM) observation showed that ASURA is required for proper kinetochore formation. By the partial depletion of ASURA, kinetochore maturation is impaired, and kinetochores showing fibrillar balls without a well-defined outer plates are often observed. Moreover, even when the outer plates of kinetochores are constructed, most showed structures stretched and/or distended from the centromere, which resembled premature kinetochores at prometaphase, indicating that the constructed kinetochore plates are less rigid against tension derived from kinetochore microtubule pulling forces. We concluded that ASURA is an essential protein for complete kinetochore development, although ASURA is not being integrated to the kinetochore. These results highlight the uniqueness of ASURA as a kinetochore protein.
ASURA(PHB2)敲低已被证实会导致姐妹染色单体过早失去着丝粒黏合,并破坏几个外板蛋白向动粒的定位。结果,细胞在有丝分裂期停滞,染色体无法向中期板汇聚。在这项研究中,我们进一步阐明了 ASURA 对染色体汇聚功能的作用机制。有趣的是,与构成动粒的其他动粒蛋白不同,ASURA 在有丝分裂期间并不特异性地定位于动粒。电子显微镜(EM)观察显示,ASURA 是适当的动粒形成所必需的。通过 ASURA 的部分耗竭,动粒成熟受损,经常观察到显示出纤维状球而没有明确的外板的动粒。此外,即使构建了动粒的外板,大多数也表现出从着丝粒伸展和/或膨胀的结构,类似于早前期的不成熟动粒,表明构建的动粒板对来自动粒微管拉力的张力的刚性较小。我们得出结论,ASURA 是完整动粒发育所必需的蛋白,尽管 ASURA 未整合到动粒中。这些结果突出了 ASURA 作为动粒蛋白的独特性。