Cell Motility Laboratory, Cancer Research UK, London Research Institute, London WC2A 3LY, UK.
Cell Host Microbe. 2012 Sep 13;12(3):346-59. doi: 10.1016/j.chom.2012.08.002.
During their egress, newly assembled vaccinia virus particles fuse with the plasma membrane and enhance their spread by inducing Arp2/3-dependent actin polymerization. Investigating the events surrounding vaccinia virus fusion, we discovered that vaccinia transiently recruits clathrin in a manner dependent on the clathrin adaptor AP-2. The recruitment of clathrin to vaccinia dramatically enhances the ability of the virus to induce actin-based motility. We demonstrate that clathrin promotes clustering of the virus actin tail nucleator A36 and host N-WASP, which activates actin nucleation through the Arp2/3 complex. Increased clustering enhances N-WASP stability, leading to more efficient actin tail initiation and sustained actin polymerization. Our observations uncover an unexpected role for clathrin during virus spread and have important implications for the regulation of actin polymerization.
在出芽过程中，新组装的痘病毒颗粒与质膜融合，并通过诱导 Arp2/3 依赖性肌动蛋白聚合来增强其扩散。在研究痘病毒融合相关事件时，我们发现痘病毒以依赖于网格蛋白衔接蛋白 AP-2 的方式瞬时募集网格蛋白。网格蛋白募集到痘病毒上显著增强了病毒诱导基于肌动蛋白的运动的能力。我们证明，网格蛋白促进病毒肌动蛋白尾部成核因子 A36 和宿主 N-WASP 的聚集，通过 Arp2/3 复合物激活肌动蛋白成核。聚集增加增强了 N-WASP 的稳定性，导致更有效的肌动蛋白尾起始和持续的肌动蛋白聚合。我们的观察结果揭示了网格蛋白在病毒传播过程中的一个意外作用，对肌动蛋白聚合的调节具有重要意义。
