Petronczki Mark, Glotzer Michael, Kraut Norbert, Peters Jan-Michael
Research Institute of Molecular Pathology, A-1030 Vienna, Austria.
Dev Cell. 2007 May;12(5):713-25. doi: 10.1016/j.devcel.2007.03.013.
Cytokinesis of animal cells requires ingression of the actomyosin-based contractile ring between segregated sister genomes. Localization of the RhoGEF Ect2 to the central spindle at anaphase promotes local activation of the RhoA GTPase, which induces assembly and ingression of the contractile ring. Here we have used BI 2536, an inhibitor of the mitotic kinase Plk1, to analyze the functions of this enzyme during late mitosis in human cells. We show that Plk1 acts after Cdk1 inactivation and independently from Aurora B to promote RhoA accumulation at the equator, contractile ring formation, and cleavage furrow ingression. Inhibition of Plk1 abolishes the interaction of Ect2 with its activator and midzone anchor, HsCyk-4, thereby preventing localization of Ect2 to the central spindle. We propose that late mitotic Plk1 activity promotes recruitment of Ect2 to the central spindle, triggering the initiation of cytokinesis and contributing to cleavage plane specification in human cells.
动物细胞的胞质分裂需要基于肌动球蛋白的收缩环在分离的姐妹基因组之间向内凹陷。后期时，RhoGEF Ect2定位于中央纺锤体，促进RhoA GTP酶的局部激活，从而诱导收缩环的组装和向内凹陷。在此，我们使用有丝分裂激酶Plk1的抑制剂BI 2536来分析该酶在人类细胞有丝分裂后期的功能。我们发现，Plk1在Cdk1失活后发挥作用，且独立于Aurora B，以促进RhoA在赤道面的积累、收缩环的形成以及分裂沟的向内凹陷。抑制Plk1会消除Ect2与其激活剂和中带锚定蛋白HsCyk-4的相互作用，从而阻止Ect2定位于中央纺锤体。我们提出，有丝分裂后期的Plk1活性促进Ect2募集至中央纺锤体，触发胞质分裂的起始，并有助于确定人类细胞的分裂平面。
