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© The Rockefeller University Press, 0021-9525/2002/8/617 $5.00
The Journal of Cell Biology, Volume 158, Number 4, August 19, 2002 617-623

Human TPX2 is required for targeting Aurora-A kinase to the spindle

¹ Max Planck Institute of Biochemistry, Department of Cell Biology, D-82152 Martinsried, Germany
² European Molecular Biology Laboratory, D-69117 Heidelberg, Germany

Address correspondence to Erich A. Nigg, Max Planck Institute of Biochemistry, Dept. of Cell Biology, Am Klopferspitz 18a, D-82152 Martinsried, Germany. Tel.: 49-89-8578-3100. Fax: 49-89-8578-3102. E-mail: nigg{at}biochem.mpg.de

Aurora-A is a serine-threonine kinase implicated in the assembly and maintenance of the mitotic spindle. Here we show that human Aurora-A binds to TPX2, a prominent component of the spindle apparatus. TPX2 was identified by mass spectrometry as a major protein coimmunoprecipitating specifically with Aurora-A from mitotic HeLa cell extracts. Conversely, Aurora-A could be detected in TPX2 immunoprecipitates. This indicates that subpopulations of these two proteins undergo complex formation in vivo. Binding studies demonstrated that the NH₂ terminus of TPX2 can directly interact with the COOH-terminal catalytic domain of Aurora-A. Although kinase activity was not required for this interaction, TPX2 was readily phosphorylated by Aurora-A. Upon siRNA-mediated elimination of TPX2 from cells, the association of Aurora-A with the spindle microtubules was abolished, although its association with spindle poles was unaffected. Conversely, depletion of Aurora-A by siRNA had no detectable influence on the localization of TPX2. We propose that human TPX2 is required for targeting Aurora-A kinase to the spindle apparatus. In turn, Aurora-A might regulate the function of TPX2 during spindle assembly.

Key Words: spindle; mitosis; Aurora-A; TPX2; siRNA

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