Biozentrum, Universität Würzburg, Würzburg, Germany.
J Cell Sci. 2012 May 15;125(Pt 10):2393-406. doi: 10.1242/jcs.097253. Epub 2012 Feb 17.
The mammalian DREAM complex is a key regulator of cell-cycle-regulated gene transcription and drives the expression of many gene products required for mitosis and cytokinesis. In this study, we characterized GAS2L3, which belongs to the GAS2 family of proteins with putative actin- and microtubule-binding domains as a target gene of DREAM. We found that GAS2L3 localizes to the spindle midzone and the midbody during anaphase and cytokinesis, respectively. Biochemical studies show that GAS2L3 binds to and bundles microtubules as well as F-actin in vitro. Strikingly, the RNAi-mediated knockdown of GAS2L3 results in chromosome segregation defects in multinucleated cells and in cells with multi-lobed nuclei. Likewise, chronic downregulation of GAS2L3 causes chromosome loss and aneuploidy. Time-lapse videomicroscopy experiments in GAS2L3-knockdown cells reveal abnormal oscillation of chromatin and the spindle during cytokinesis. Taken together, our data reveal novel, important roles of GAS2L3 for faithful cell division. Our work thus contributes to the understanding of how DREAM regulates cytokinesis.
哺乳动物的 DREAM 复合物是细胞周期调控基因转录的关键调节剂，它驱动有丝分裂和胞质分裂所需的许多基因产物的表达。在这项研究中，我们将 GAS2L3 鉴定为 DREAM 的靶基因，GAS2L3 属于具有潜在肌动蛋白和微管结合结构域的 GAS2 蛋白家族。我们发现 GAS2L3 在有丝分裂后期和胞质分裂过程中分别定位于纺锤体中部和中部。生化研究表明 GAS2L3 能够在体外结合并束微管和 F-肌动蛋白。引人注目的是，GAS2L3 的 RNAi 介导的敲低会导致多核细胞和多叶核细胞中的染色体分离缺陷。同样，GAS2L3 的慢性下调会导致染色体丢失和非整倍体。在 GAS2L3 敲低细胞中的延时视频显微镜实验揭示了胞质分裂过程中染色质和纺锤体的异常摆动。总之，我们的数据揭示了 GAS2L3 对于忠实细胞分裂的新的、重要作用。我们的工作有助于理解 DREAM 如何调节胞质分裂。
