buylotrogold

Monica Hoyos Flight1 . The bipolar organization of the mitotic spindle is essential for the proper segregation of chromosomes during cell division. The serine and threonine kinase Polo-like kinase-1 (Plk1) has a key role in bipolar spindle formation, but its mechanism of action was unknown until now. Reporting in Nature Cell Biology, Oshimori et al. have identified Kizuna (Kiz) as a Plk1 substrate that maintains centrosome integrity and spindle bipolarity. Upon cell division, centrosomes - the main microtubule-organizing centres in cells - duplicate and separate to define the spindle poles. Each centrosome consists of a pair of centrioles surrounded by a cloud of pericentriolar materials (PCM) that facilitate microtubule nucleation and anchoring. Kiz, a new Plk1 substrate that was identified in a solid-phase phosphorylation screen, localizes to centrosomes and the centrosome-surrounding area. RNA interference (RNAi)-mediated depletion of Kiz leads to a striking multipolar spindle phenotype in which PCM is dissociated from centrioles at pro_meta_phase. Surprisingly, this effect was not due to defects in centrosome amplification or centriole fragmentation. Instead, PCM proteins were found to accumulate at all spindle poles regardless of whether centrioles were present. ...Plk1-mediated phosphorylation of Kiz protects centrosomes from collapse... Microtubule-mediated forces that act on centrosomes are known to induce centriole collapse and disrupt spindle bipolarity. When these forces were attenuated by depleting the chromokinesin Kid, the effects of Kiz depletion on spindle bipolarity were decreased. This finding indicates that Kiz helps centrosomes endure the mechanical forces that are exerted on them by microtubules. Oshimori et al. also showed that Plk1 phosphorylates Kiz on Thr379 specifically during mitosis. Whereas the _expression_ of a phosphomimetic mutant of Kiz could partially restore bipolar spindles in Plk1-depleted cells, wild-type Kiz was unable to rescue the effects of Plk1 knockdown, indicating that Plk1-mediated phosphorylation of Kiz is necessary for spindle-pole stabilization. As the phosphorylation of Kiz increases its association with a subset of PCM components, the authors propose that, by stabilizing interactions between centrioles and the PCM, Plk1-mediated phosphorylation of Kiz protects centrosomes from collapse and ensures bipolar spindle formation. Unlike Plk1 depletion, which causes pro_meta_phase arrest, cells that lack Kiz exit mitosis with multiple or malformed nuclei. The additional effects of Plk1 on chromosome segregation and cytokinesis are likely to be mediated by other substrates; however, the identification of Kiz is the first step towards unravelling the mechanism of action of Plk1.