Centrobin regulates the assembly of functional mitotic spindles
Centrobin regulates the assembly of functional mitotic spindles
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DOI：
10.1038/onc.2010.37
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发表时间：
2010-05-06
期刊：
影响因子：
8
通讯作者：
Khanna, K. K.
中科院分区：
文献类型：
--
作者：
Jeffery, J. M.;Urquhart, A. J.;Khanna, K. K.
纺锤体的适当功能对于染色体分离的高保真度至关重要，并且对于人类肿瘤抑制是不可或缺的。Centrobin是最近发现的一种中心体蛋白，具有稳定微管结构的作用。在这里，我们功能上的缺陷，在中心体的完整性和纺锤体组装Centrobin耗尽的细胞。Centrobin缺失的细胞表现出一系列纺锤体异常，包括与中心体无关的非聚焦极、S形纺锤体和迷你纺锤体。这些细胞经历有丝分裂停滞，随后通常通过凋亡而死亡，如通过活细胞成像所确定的。Mad 2的共耗竭缓解了有丝分裂停滞，表明细胞停滞是由于未能沉默中期的纺锤体检查点。与此一致，Centrobin耗尽的中期细胞对BubR 1和BubR 1 S676染色呈阳性。用一组中心体标记物染色显示中心体锚定到有丝分裂纺锤体的丢失。此外，这些细胞显示出较少的冷稳定微管和动粒对之间的较短距离。这些结果表明Centrobin在维持中心体完整性方面是必需的，这反过来又促进有丝分裂纺锤体锚定到中心体。此外，这种锚定是微管-动粒附着的稳定性和张力驱动的有丝分裂纺锤体的生物发生所必需的。Oncogene（2010）29，2649-2658; doi：10.1038/onc.2010.37; 2010年3月1日在线发表
The proper function of the spindle is crucial to the high fidelity of chromosome segregation and is indispensable for tumor suppression in humans. Centrobin is a recently identified centrosomal protein that has a role in stabilizing the microtubule structure. Here we functionally characterize the defects in centrosome integrity and spindle assembly in Centrobin-depleted cells. Centrobin-depleted cells show a range of spindle abnormalities including unfocused poles that are not associated with centrosomes, S-shaped spindles and mini spindles. These cells undergo mitotic arrest and subsequently often die by apoptosis, as determined by live cell imaging. Co-depletion of Mad2 relieves the mitotic arrest, indicating that cells arrest due to a failure to silence the spindle checkpoint in metaphase. Consistent with this, Centrobin-depleted metaphase cells stained positive for BubR1 and BubR1 S676. Staining with a panel of centrosome markers showed a loss of centrosome anchoring to the mitotic spindle. Furthermore, these cells show less cold-stable microtubules and a shorter distance between kinetochore pairs. These results show a requirement of Centrobin in maintaining centrosome integrity, which in turn promotes anchoring of mitotic spindle to the centrosomes. Furthermore, this anchoring is required for the stability of microtubule-kinetochore attachments and biogenesis of tension-ridden and properly functioning mitotic spindle. Oncogene (2010) 29, 2649-2658; doi:10.1038/onc.2010.37; published online 1 March 2010