Stable kinetochore-microtubule interactions depend on the Ska complex and its new component Ska3/C13Orf3.

Stable kinetochore-microtubule interactions depend on the Ska complex and its new component Ska3/C13Orf3.
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DOI:
10.1038/emboj.2009.96
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发表时间:
2009-05-20
期刊:
影响因子:
11.4
通讯作者:
Nigg, Erich A.
Nigg, Erich A.
中科院分区:
生物学1区
文献类型:
--
作者:
Gaitanos, Thomas N.;Santamaria, Anna;Jeyaprakash, A. Arockia;Wang, Bin;Conti, Elena;Nigg, Erich A.

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Ska 1和Ska 2在着丝粒-微管(KT-MT)界面处形成复合物,并且是从中期到后期及时进展所必需的。在这里,我们使用质谱法来寻找斯卡复合物的其他成分。我们确定C13 Orf 3(现在称为Ska 3)作为一个新的成员,这个复杂的和映射的三个已知组件之间的相互作用域。Ska 3具有与Ska 1和Ska 2相似的特性:在整个有丝分裂过程中,Ska 3定位于纺锤体和KT,其缺失显著延迟后期转换。有趣的是,伴随Ska 1和Ska 3的耗竭,更完全地去除Ska复合物导致染色体聚集失败,随后细胞死亡。这种严重的表型反映了KT-MT相互作用的不稳定性,如KT纤维的冷稳定性降低所证明的。然而,SKA复合物的耗尽仅轻微地损害负责MT附着的KMN网络的KT定位。我们建议,斯卡复杂的功能补充KMN,提供了一个额外的层的稳定性KT-MT附件和可能的信号完成附件的纺锤体检查点。
Ska1 and Ska2 form a complex at the kinetochore–microtubule (KT–MT) interface and are required for timely progression from metaphase to anaphase. Here, we use mass spectrometry to search for additional components of the Ska complex. We identify C13Orf3 (now termed Ska3) as a novel member of this complex and map the interaction domains among the three known components. Ska3 displays similar characteristics as Ska1 and Ska2: it localizes to the spindle and KT throughout mitosis and its depletion markedly delays anaphase transition. Interestingly, a more complete removal of the Ska complex by concomitant depletion of Ska1 and Ska3 results in a chromosome congression failure followed by cell death. This severe phenotype reflects a destabilization of KT–MT interactions, as demonstrated by reduced cold stability of KT fibres. Yet, the depletion of the Ska complex only marginally impairs KT localization of the KMN network responsible for MT attachment. We propose that the Ska complex functionally complements the KMN, providing an additional layer of stability to KT–MT attachment and possibly signalling completion of attachment to the spindle checkpoint.
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