Khmelinskii Anton, Roostalu Johanna, Roque Helio, Antony Claude, Schiebel Elmar
Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz, Im Neuenheiemer Feld 282, Heidelberg 69117, Germany.
Dev Cell. 2009 Aug;17(2):244-56. doi: 10.1016/j.devcel.2009.06.011.
The metaphase-to-anaphase transition is one of the most dramatic and highly regulated steps in cell division. At anaphase onset the protease separase dissolves sister chromatid cohesion. Simultaneously, the mitotic spindle elongates as interpolar microtubules (iMTs) slide apart at the spindle midzone, ensuring chromosome segregation. However, it remains unclear how spindle elongation is coordinated with cell cycle progression. Here we demonstrate that phosphorylation of the midzone organizer Ase1 controls localization and function of Cin8, a kinesin-5 that slides iMTs relative to each other. Phosphorylation of Ase1 by Cdk1 (cyclin-dependent kinase) inhibits Cin8 binding to iMTs, preventing bending and collapse of the metaphase spindle. In anaphase Ase1 dephosphorylation by the separase-activated phosphatase Cdc14 is necessary and sufficient for Cin8 recruitment to the midzone, where it drives spindle elongation. Our results reveal that sliding forces at the midzone are activated by separase and explain how spindle elongation is triggered with anaphase entry.
中期到后期的转变是细胞分裂过程中最剧烈且受到高度调控的步骤之一。在后期开始时，蛋白酶分离酶会溶解姐妹染色单体的黏连。与此同时，有丝分裂纺锤体随着极间微管（iMTs）在纺锤体中区相互滑动而伸长，确保染色体分离。然而，纺锤体伸长如何与细胞周期进程协调仍不清楚。在这里，我们证明了中区组织者Ase1的磷酸化控制着Cin8的定位和功能，Cin8是一种驱动iMTs相互滑动的驱动蛋白-5。细胞周期蛋白依赖性激酶Cdk1对Ase1的磷酸化抑制了Cin8与iMTs的结合，防止中期纺锤体弯曲和塌陷。在后期，分离酶激活的磷酸酶Cdc14对Ase1的去磷酸化对于Cin8募集到中区是必要且充分的，在中区它驱动纺锤体伸长。我们的结果揭示了中区的滑动力是由分离酶激活的，并解释了纺锤体伸长是如何随着后期进入而触发的。
