Mitotic chromatin regulates phosphorylation of Stathmin/Op18

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 exclusive(1-3). The 'search and capture' model suggests that dynamic microtubules become progressively captured and stabilized by the kinetochores on chromosomes, leading to spindle assembly(3,4). The 'local stabilization' model proposes that chromosomes change the state of the cytoplasm around them, making it more favourable to microtubule polymerization(2,5-9). It has been shown(10,11) that Stathmin/Op18 inhibits microtubule polymerization in vitro by interaction with tubulin(12), and that overexpression in tissue culture cells of non-phosphorylatable mutants of Stathmin/Op18 prevents the assembly of mitotic spindles(13). We have used Xenopus egg extracts and magnetic chromatin beads(14) to show that mitotic chromatin induces phosphorylation of Stathmin/Op18. We have also shown the Stathmin/Op18 is one of the factors regulated by mitotic chromatin that governs preferential microtubule growth around chromosomes during spindle assembly.