Lipid Biology Laboratory, RIKEN Advanced Science Institute, Wako, Saitama, Japan.
Mol Cell Biol. 2012 Apr;32(8):1396-407. doi: 10.1128/MCB.06113-11. Epub 2012 Feb 13.
Cytokinesis is a crucial step in the creation of two daughter cells by the formation and ingression of the cleavage furrow. Here, we show that sphingomyelin (SM), one of the major sphingolipids in mammalian cells, is required for the localization of phosphatidylinositol-4,5-bisphosphate (PIP(2)) to the cleavage furrow during cytokinesis. Real-time observation with a labeled SM-specific protein, lysenin, revealed that SM is concentrated in the outer leaflet of the furrow at the time of cytokinesis. Superresolution fluorescence microscopy analysis indicates a transbilayer colocalization between the SM-rich domains in the outer leaflet and PIP(2)-rich domains in the inner leaflet of the plasma membrane. The depletion of SM disperses PIP(2) and inhibits the recruitment of the small GTPase RhoA to the cleavage furrow, leading to abnormal cytokinesis. These results suggest that the formation of SM-rich domains is required for the accumulation of PIP(2) to the cleavage furrow, which is a prerequisite for the proper translocation of RhoA and the progression of cytokinesis.
胞质分裂是通过形成和内陷的分裂沟将两个子细胞分裂的关键步骤。在这里，我们表明，鞘磷脂（SM），哺乳动物细胞中主要的鞘脂之一，在胞质分裂过程中，将磷脂酰肌醇-4,5-二磷酸（PIP（2））定位到分裂沟是必需的。用标记的 SM 特异性蛋白溶菌素进行实时观察显示，SM 在胞质分裂时集中在沟的外叶。超分辨率荧光显微镜分析表明，在外叶富含 SM 的区域与质膜内叶富含 PIP（2）的区域之间存在跨双层共定位。SM 的耗竭会分散 PIP（2）并抑制小 GTPase RhoA 向分裂沟的募集，导致异常的胞质分裂。这些结果表明，富含 SM 的域的形成对于 PIP（2）向分裂沟的积累是必需的，这是 RhoA 的正确易位和胞质分裂进展的前提。
