A dynamin-cortactin-Arp2/3 complex mediates actin reorganization in growth factor-stimulated cells
A dynamin-cortactin-Arp2/3 complex mediates actin reorganization in growth factor-stimulated cells
复制标题
DOI：
10.1091/mbc.e02-08-0466
复制
发表时间：
2003-03-01
影响因子：
3.3
通讯作者：
McNiven, MA
中科院分区：
文献类型：
--
作者：
Krueger, EW;Orth, JD;McNiven, MA
哺乳动物细胞在运动刺激下重塑肌动蛋白细胞骨架的机制是复杂的，也是一个深入研究的课题。发动蛋白2（Dyn 2）是一种大的GTdR，其直接与包括core-binding蛋白在内的几种肌动蛋白结合蛋白相互作用。在这项研究中，我们证明，Dyn 2和corpine功能介导的肌动蛋白细胞骨架的动态重塑与运动生长因子血小板衍生生长因子的刺激。在刺激下，Dyn 2和corneumen在背侧细胞表面共同组装成大的圆形结构。这些“波”促进前细胞质中肌动蛋白丝的主动重组，并起到分解肌动蛋白应力纤维的作用。重要的是，抑制Dyn 2和corpine功能有效地阻止了波的形成和随后的肌动蛋白重组。这些研究结果表明，corneum和Dyn 2功能在一个超分子复合物，组装在响应生长因子的刺激和介导的肌动蛋白的重塑，以促进在迁移细胞的前缘板状伪足突起。
The mechanisms by which mammalian cells remodel the actin cytoskeleton in response to motogenic stimuli are complex and a topic of intense study. Dynamin 2 (Dyn2) is a large GTPase that interacts directly with several actin binding proteins, including cortactin. In this study, we demonstrate that Dyn2 and cortactin function to mediate dynamic remodeling of the actin cytoskeleton in response to stimulation with the motogenic growth factor platelet-derived growth factor. On stimulation, Dyn2 and cortactin coassemble into large, circular structures on the dorsal cell surface. These "waves" promote an active reorganization of actin filaments in the anterior cytoplasm and function to disassemble actin stress fibers. Importantly, inhibition of Dyn2 and cortactin function potently blocked the formation of waves and subsequent actin reorganization. These findings demonstrate that cortactin and Dyn2 function together in a supramolecular complex that assembles in response to growth factor stimulation and mediates the remodeling of actin to facilitate lamellipodial protrusion at the leading edge of migrating cells.