PMID: 18414060Apr 17, 2008Paper

Requirement of aurora-A kinase in astral microtubule polymerization and spindle microtubule flux

Cell Cycle
Li-hui WangQuentin Liu

Abstract

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 microt...Continue Reading

Citations

Jun 13, 2012·The Journal of Biological Chemistry·Yuji NakayamaNaoto Yamaguchi
Jan 15, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Umesh K JinwalChad A Dickey
Apr 2, 2009·Expert Opinion on Investigational Drugs·Chun Hei Antonio CheungJang-Yang Chang
Apr 1, 2009·Experimental Cell Research·Shi-Mun KimSun-Ho Kee
Aug 8, 2015·Molecular Biology of the Cell·Sara CarvalhalEric R Griffis

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