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Vol. 17, Issue 4, 2069-2080, April 2006

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Ran Is Required before Metaphase for Spindle Assembly and Chromosome Alignment and after Metaphase for Chromosome Segregation and Spindle Midbody Organization

Department of Medical Genetics and Microbiology, University of Toronto, M5S 1A8 Toronto, Ontario, Canada

Submitted October 28, 2005; Accepted February 3, 2006
Monitoring Editor: Yixian Zheng

The Ran pathway has been shown to have a role in spindle assembly. However, the extent of the role of the Ran pathway in mitosis in vivo is unclear. We report that perturbation of the Ran pathway disrupted multiple steps of mitosis in syncytial Drosophila embryos and uncovered new mitotic processes that are regulated by Ran. During the onset of mitosis, the Ran pathway is required for the production, organization, and targeting of centrosomally nucleated microtubules to chromosomes. However, the role of Ran is not restricted to microtubule organization, because Ran is also required for the alignment of chromosomes at the metaphase plate. In addition, the Ran pathway is required for postmetaphase events, including chromosome segregation and the assembly of the microtubule midbody. The Ran pathway mediates these mitotic events, in part, by facilitating the correct targeting of the kinase Aurora A and the kinesins KLP61F and KLP3A to spindles.

Abbreviations used: MT, microtubule; NLS, nuclear localization signal; NTR, nuclear transport receptor; SAF, spindle assembly factor.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Andrew Wilde (andrew.wilde{at}utoronto.ca).

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