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

被引:180
作者
Gaitanos, Thomas N. [1 ]
Santamaria, Anna [1 ]
Jeyaprakash, A. Arockia [2 ]
Wang, Bin [1 ]
Conti, Elena [2 ]
Nigg, Erich A. [1 ,3 ]
机构
[1] Max Planck Inst Biochem, Dept Cell Biol, D-82152 Martinsried, Germany
[2] Max Planck Inst Biochem, Dept Struct Cell Biol, D-82152 Martinsried, Germany
[3] Univ Basel, Biozentrum, Basel, Switzerland
关键词
chromosome congression; kinetochore; microtubule-attachment; mitosis; SPINDLE-ASSEMBLY CHECKPOINT; HUMAN MITOTIC SPINDLE; RNA EXPORT FACTOR; TYROSINE PHOSPHORYLATION; PHOSPHOPROTEOME ANALYSIS; CHROMOSOME ALIGNMENT; OUTER KINETOCHORE; CELLS; PROTEIN; ATTACHMENT;
D O I
10.1038/emboj.2009.96
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. The EMBO Journal (2009) 28, 1442-1452. doi:10.1038/emboj.2009.96; Published online 9 April 2009
引用
收藏
页码:1442 / 1452
页数:11
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