Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA.
Dev Cell. 2009 Dec;17(6):811-22. doi: 10.1016/j.devcel.2009.11.005.
The GTPase dynamin, a key player in endocytic membrane fission, interacts with numerous proteins that regulate actin dynamics and generate/sense membrane curvature. To determine the functional relationship between these proteins and dynamin, we have analyzed endocytic intermediates that accumulate in cells that lack dynamin (derived from dynamin 1 and 2 double conditional knockout mice). In these cells, actin-nucleating proteins, actin, and BAR domain proteins accumulate at the base of arrested endocytic clathrin-coated pits, where they support the growth of dynamic long tubular necks. These results, which we show reflect the sequence of events in wild-type cells, demonstrate a concerted action of these proteins prior to, and independent of, dynamin and emphasize similarities between clathrin-mediated endocytosis in yeast and higher eukaryotes. Our data also demonstrate that the relationship between dynamin and actin is intimately connected to dynamin's endocytic role and that dynamin terminates a powerful actin- and BAR protein-dependent tubulating activity.
GTP 酶动力蛋白是胞吞作用中膜裂变的关键参与者，它与许多调节肌动蛋白动力学并产生/感知膜曲率的蛋白质相互作用。为了确定这些蛋白质与动力蛋白之间的功能关系，我们分析了在缺乏动力蛋白的细胞中积累的胞吞作用中间产物（来源于动力蛋白 1 和 2 双条件敲除小鼠）。在这些细胞中，肌动蛋白成核蛋白、肌动蛋白和 BAR 结构域蛋白在被阻断的网格蛋白包被陷窝的底部积累，在那里它们支持动态长管状颈部的生长。我们展示的这些结果反映了野生型细胞中事件的顺序，证明了这些蛋白质在动力蛋白之前和独立于动力蛋白的协同作用，并强调了酵母和高等真核生物中网格蛋白介导的胞吞作用之间的相似性。我们的数据还表明，动力蛋白与肌动蛋白之间的关系与动力蛋白的胞吞作用密切相关，并且动力蛋白终止了强大的肌动蛋白和 BAR 蛋白依赖性管状活性。
