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Coordination of Chromosome Alignment and Mitotic Progression Chromosome-Based Ran Signal

Hoi Y. Li, Win Pin Ng, Wong Chi Hang, Pablo A. Iglesias and Yixian Zheng

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Mitotic spindle assembly and chromosome segregation are controlled by the cell cycle machinery and by the guanosine triphosphatase Ran (RanGTPase). We developed a spatial model that allows us to simulate RanGTP production with different degrees of chromosome alignment in mitosis. Aided by this model, we defined three factors that modulate mitotic RanGTP gradients and mitotic progression in somatic cells. First, the concentration of RanGTPtransport-receptor (represented by RanGTP-importin β) and its spatial distribution are very sensitive to the level of RanBP1. Reduction of RanBP1 leads to an elevated RanGTP-transport receptor concentration throughout the cell, which disrupts spindle assembly and weakens spindle checkpoint control. Second, the completion of chromosome alignment at the metaphase plate generates highest local RanGTP concentrations on chromosomes that could lead to spindle checkpoint silencing and metaphase-anaphase transition. Finally, chromosomal RanGTP production could be dampened by a reduction of RCC1 phosphorylation in mitosis. Our spatial simulation of RanGTP production using individual chromosomes should provide means to further understand how the Ran system and the cell cycle machinery coordinately regulate mitosis.

Authors

Hoi Y. Li

Howard Hughes Medical Institute; Baltimore, Maryland

Win Pin Ng

Johns Hopkins University; Baltimore, Maryland

Wong Chi Hang

Nanyang Technological University; Singapore

Pablo A. Iglesias

Johns Hopkins University Whiting School of Engineering, Baltimore, MD

Yixian Zheng

Carnegie Institution of Washington and Howard Hughes Medical Institute, Baltimore, Maryland

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If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.