PDF(Pubmed)
Abstract：
Accurate chromosome segregation in mitosis depends on multiprotein structures called kinetochores that are built on the centromeric region of sister chromatids and serve to capture mitotic spindle microtubules. In early mitosis, unattached kinetochores expand a crescent-shaped structure called fibrous corona whose function is to facilitate initial kinetochore-microtubule attachments and chromosome transport by microtubules. Subsequently, the fibrous corona must be timely disassembled to prevent segregation errors. Although recent studies provided new insights on the molecular content and mechanism of fibrous corona assembly, it remains unknown what triggers the disassembly of the outermost and dynamic layer of the kinetochore. Here, we show that Aurora A and B kinases phosphorylate CENP-E to release it from an autoinhibited state. At kinetochores, Aurora B phosphorylates CENP-E to prevent its premature removal together with other corona proteins by dynein. At the spindle poles, Aurora A phosphorylates CENP-E to promote chromosome congression and prevent accumulation of corona proteins at the centrosomes, allowing for their intracellular redistribution. Thus, we propose the Aurora A/B-CENP-E axis as a critical element of the long-sought-for mechanism of fibrous corona disassembly that is essential for accurate chromosome segregation.
摘要：
有丝分裂中的准确染色体分离取决于称为动子的多蛋白结构，该结构建立在姐妹染色单体的着丝粒区域上，并用于捕获有丝分裂纺锤体微管。在早期有丝分裂中，未附着的动静脉扩张了月牙形结构，称为纤维电晕，其功能是促进最初的动静脉-微管附着和微管的染色体运输。随后，纤维电晕必须及时拆卸，以防止偏析错误。尽管最近的研究为纤维电晕组装的分子含量和机理提供了新的见解，尚不清楚是什么触发了动子的最外层和动态层的拆卸。这里,我们显示AuroraA和B激酶磷酸化CENP-E，使其从自抑制状态释放。在kinetochores，极光B磷酸化CENP-E，以防止其与其他电晕蛋白一起被动力蛋白过早去除。在主轴杆处，AuroraA磷酸化CENP-E以促进染色体拥塞并防止电晕蛋白在中心体的积累，允许它们在细胞内重新分布。因此，我们建议将AuroraA/B-CENP-E轴作为长期寻求的纤维电晕分解机制的关键元素，这对于准确的染色体分离至关重要。
