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Mitotic chromatin regulates phosphorylation of Stathmin/Op18

Abstract

Meiotic and mitotic spindles are required for the even segregation of duplicated chromosomes to the two daughter cells. The mechanism of spindle assembly is not fully understood, but two have been proposed that are not mutually exclusive1,2,3. The ‘search and capture’ model suggests that dynamic microtubules become progressively captured and stabilized by the kinetochores on chromosomes, leading to spindle assembly3,4. The ‘local stabilization’ model proposes that chromosomes change the state of the cytoplasm around them, making it more favourable to microtubule polymerization2,5,6,7,8,9. It has been shown10,11 that Stathmin/Op18 inhibits microtubule polymerization in vitro by interaction with tubulin12, and that overexpression in tissue culture cells of non-phosphorylatable mutants of Stathmin/Op18 prevents the assembly of mitotic spindles13. We have used Xenopus egg extracts and magnetic chromatin beads14 to show that mitotic chromatin induces phosphorylation of Stathmin/Op18. We have also shown that Stathmin/Op18 is one of the factors regulated by mitotic chromatin that governs preferential microtubule growth around chromosomes during spindle assembly.

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Figure 1: Hyperphosphorylation of Stathmin/Op18 during mitosis requires mitotic chromatin.
Figure 2: A type 2A phosphatase regulates Stathmin/Op18 phosphorylation.
Figure 3: Stathmin/Op18 is phosphorylated mainly on the Cdc2 site in mitosis.
Figure 4: Mutant Stathmin/Op18 causes rapid shortening of the mitotic spindle.

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Acknowledgements

We thank D. Chrétien, K. Dejgaard, J. Domínguez, R. Heald, J. Howard, T. J. Mitchison, I. T. Möst, A. Nebreda, M. Way, T. Wittmann and M. Zerial for discussions and reagents.

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Correspondence to Søren S. L. Andersen.

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Andersen, S., Ashford, A., Tournebize, R. et al. Mitotic chromatin regulates phosphorylation of Stathmin/Op18. Nature 389, 640–643 (1997). https://doi.org/10.1038/39382

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