Requirement of Aurora-A kinase in astral microtubule polymerization and spindle microtubule flux
Requirement of Aurora-A kinase in astral microtubule polymerization and spindle microtubule flux
复制标题
星体微管聚合和纺锤体微管通量中 Aurora-A 激酶的需求
DOI：
10.4161/cc.7.8.5738
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发表时间：
2008
期刊：
影响因子：
4.3
通讯作者：
Quentin Liu
中科院分区：
文献类型：
--
作者：
Li;M. Yan;Da;Jun;Xiao;Y. Zeng;Quentin Liu
有丝分裂Aurora-A激酶被发现是形成双极纺锤体所必需的，确保有丝分裂中染色体的准确分离。最近，Aurora-A被证明可以促进ran - gtp诱导的纺锤体形成和星状微管的发育。在这里，通过选择性免疫缺失，我们发现在非洲爪蟾卵提取物中中心体诱导的星状微管形成需要Aurora-A，而不是ran - gtp诱导的。Aurora-A增强了中心体和ran - gtp诱导的aster组装中的微管聚合：缩短了aster组装的时间，增加了aster的尺寸。事实上，单独添加Aurora- a蛋白会诱导微管聚集，而极光激酶抑制小分子ZM447439会消除微管聚集。此外，我们发现极光- a对于ran - gtp诱导的双极纺锤体形成是必不可少的。通过添加激酶失活显性突变体抑制Aurora-A活性导致纺锤体坍塌和单极纺锤体形成，而负端运动蛋白dynein/dynactin抑制剂p50/dynamitin挽救了双极结构。最后，我们发现极光- a是微管向极地流动所必需的，这种需求取决于激酶活性。因此，我们证明了Aurora-A促进微管聚合并维持微管通量，以确保适当的双极主轴组装。
Mitotic Aurora-A kinase was found to be required for formation of bipolar spindle, ensuring accurate chromosome segregation in mitosis. Recently, Aurora-A was shown to promote Ran-GTP-induced spindle formation and astral microtubule development. Here, by selective immunodepletion, we showed that Aurora-A was required for centrosome- but not Ran-GTP-induced astral microtubule formation in Xenopus egg extracts. Aurora-A enhanced microtubule polymerization in both centrosome- and Ran-GTP-induced aster assemblies: shortening the timing of aster assembly and increasing the aster size. Indeed, adding of Aurora-A protein alone induced microtubule clustering, which was abrogated by Aurora kinase inhibitory small molecule ZM447439. In addition, we showed that Aurora-A was indispensable for Ran-GTP-induced bipolar spindle formation. Inhibition of Aurora-A activity by adding of kinase inactive dominant mutant led to spindle collapse and formation of monopolar spindle whereas minus-end motor protein dynein/dynactin inhibitor p50/dynamitin rescued the bipolar structure. Lastly, we revealed that Aurora-A was necessary for microtubule poleward flux and this requirement depended on kinase activity. Thus, we showed that Aurora-A promoted microtubule polymerization and maintained microtubule flux in ensuring proper bipolar spindle assembly.
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影响因子：
11.8
作者：
Portier, Nathan;Audhya, Anjon;Oegema, Karen
通讯作者：
Oegema, Karen
DOI：
10.1073/pnas.0600702103
发表时间：
2006-03-21
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
3.3
作者：
Chakravarty, A;Howard, L;Compton, DA
通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
Zheng, YX
DOI：
10.1073/pnas.0601425103
发表时间：
2006-04-11
影响因子：
11.1
作者：
Liu, Q;Ruderman, JV
通讯作者：
Ruderman, JV