Aurora B helps the central spindle measure up

Aurora B helps the central spindle measure up D uring anaphase, cells assemble a central spindle between the segregating chromosomes. Micro-tubule plus ends overlap in the middle of the cell, creating a spindle midzone that recruits factors involved in positioning the cytokinetic actomyosin ring around the cell equator. Regulating the length and organization of central spindle microtubules is therefore critical for ensuring that mitotic cells divide in the right place. Two papers reveal how the mitotic kinase Aurora B controls central spindle formation by regulating two different kinesin motor proteins (1, 2). Central spindle assembly is controlled in part by the anti-parallel microtubule-bundling protein PRC1 and its binding partner KIF4A, a kinesin motor that suppresses the growth of microtubule plus ends (3). Cyclin-dependent kinase 1 prevents premature central spindle formation by inhibiting PRC1 and other assembly factors in early mitosis. This inhibition is relieved at anaphase onset, but Francis Barr from the University of Oxford, UK, reasoned that there must also be positive signals promoting PRC1 and KIF4A's recruitment to the overlapping microtubules of the spindle midzone. " There are microtubule plus ends all over the cell. What makes those at the central spindle special? " Barr says. Barr and colleagues, led by Ricardo Nunes Bastos, found that inhibiting Au-rora B prevented KIF4A's recruitment to the spindle midzone (1). Aurora B is transported to the anaphase central spindle by the kinesin Mklp2, generating a gradient of kinase activity that radiates outwards from the spindle midzone (4, 5). Eliminating this pool of Aurora B by knocking down Mklp2 blocked KIF4A recruitment, indicating that KIF4A's localization to the central spindle is regulated by local, rather than global, levels of Aurora B activity. Aurora B phosphorylated KIF4A on a threonine residue in the kinesin's central stalk domain. Phosphorylation promoted KIF4A's localization to the central spindle by enhancing the kinesin's interaction with PRC1. But Aurora B also stimulated KIF4A's ATPase activity, which could increase the motor protein's ability to move toward the plus ends of microtubules. " The interaction with PRC1 biases KIF4A's recruitment to microtubule overlaps, " Barr explains. " It can then move toward the plus ends and shut down microtubule dynamics. " Accordingly, phosphorylated KIF4A strongly suppressed the growth of microtubules in vitro, whereas cells expressing a nonphosphorylatable version of the kinesin grew longer central spindles than cells expressing wild-type KIF4A. Barr now wants to test his model by examining how …