Lian Audrey T Y, Hains Peter G, Sarcevic Boris, Robinson Phillip J, Chircop Megan
a Children's Medical Research Institute; The University of Sydney ; Westmead , New South Wales , Australia.
Cell Cycle. 2015;14(13):2058-74. doi: 10.1080/15384101.2015.1044168. Epub 2015 Apr 30.
The final stage of mitosis is cytokinesis, which results in 2 independent daughter cells. Cytokinesis has 2 phases: membrane ingression followed by membrane abscission. IQGAP1 is a scaffold protein that interacts with proteins implicated in mitosis, including F-actin, myosin and CaM. IQGAP1 in yeast recruits actin and myosin II filaments to the contractile ring for membrane ingression. In contrast, we show that mammalian IQGAP1 is not required for ingression, but coordinates nuclear pore complex (NPC) reassembly and completion of abscission. Depletion of IQGAP1 disrupts Nup98 and mAb414 nuclear envelope localization and delays abscission timing. IQGAP1 phosphorylation increases 15-fold upon mitotic entry at S86, S330 and T1434, with the latter site being targeted by CDK2/Cyclin A and CDK1/Cyclin A/B in vitro. Expressing the phospho-deficient mutant IQGAP1-S330A impairs NPC reassembly in cells undergoing abscission. Thus, mammalian IQGAP1 functions later in mitosis than its yeast counterpart to regulate nuclear pore assembly in a S330 phosphorylation-dependent manner during the abscission phase of cytokinesis.
有丝分裂的最后阶段是胞质分裂，其结果是产生两个独立的子细胞。胞质分裂有两个阶段：膜内陷，随后是膜脱离。IQGAP1是一种支架蛋白，它与参与有丝分裂的蛋白质相互作用，包括F-肌动蛋白、肌球蛋白和钙调蛋白。酵母中的IQGAP1将肌动蛋白和肌球蛋白II细丝募集到收缩环以进行膜内陷。相比之下，我们发现哺乳动物的IQGAP1对于膜内陷不是必需的，但它协调核孔复合体（NPC）的重新组装和脱离的完成。IQGAP1的缺失会破坏Nup98和mAb414在核膜上的定位，并延迟脱离时间。在有丝分裂进入时，IQGAP1在S86、S330和T1434位点的磷酸化增加15倍，后者在体外被CDK2/细胞周期蛋白A和CDK1/细胞周期蛋白A/B靶向。表达磷酸化缺陷型突变体IQGAP1-S330A会损害正在进行脱离的细胞中的NPC重新组装。因此，哺乳动物IQGAP1在有丝分裂中的作用比酵母中的IQGAP1更靠后，在胞质分裂的脱离阶段以S330磷酸化依赖的方式调节核孔组装。
