PDF(Pubmed)
Abstract：
As the cytoskeleton sustains cell and tissue forces, it incurs physical damage that must be repaired to maintain mechanical homeostasis. The LIM-domain protein zyxin detects force-induced ruptures in actin-myosin stress fibers, coordinating downstream repair factors to restore stress fiber integrity through unclear mechanisms. Here, we reconstitute stress fiber repair with purified proteins, uncovering detailed links between zyxin\'s force-regulated binding interactions and cytoskeletal dynamics. In addition to binding individual tensed actin filaments (F-actin), zyxin\'s LIM domains form force-dependent assemblies that bridge broken filament fragments. Zyxin assemblies engage repair factors through multi-valent interactions, coordinating nucleation of new F-actin by VASP and its crosslinking into aligned bundles by ɑ-actinin. Through these combined activities, stress fiber repair initiates within the cores of micron-scale damage sites in cells, explaining how these F-actin depleted regions are rapidly restored. Thus, zyxin\'s force-dependent organization of actin repair machinery inherently operates at the network scale to maintain cytoskeletal integrity.
摘要：
细胞骨架维持细胞和组织的力量，它招致物理损伤，必须修复以保持机械稳态。LIM结构域蛋白zyxin检测肌动蛋白-肌球蛋白应力纤维中的力诱导的破裂，协调下游修复因子，通过不明确的机制恢复应力纤维完整性。这里,我们用纯化的蛋白质重建应力纤维修复，揭示酶素的力调节结合相互作用和细胞骨架动力学之间的详细联系。除了结合单个紧张的肌动蛋白丝（F-肌动蛋白），zyxin的LIM结构域形成桥断丝片段的力依赖性组装体。Zyxin组件通过多价相互作用参与修复因子，通过VASP协调新的F-肌动蛋白的成核，并通过α-actinin将其交联成对齐的束。通过这些联合活动，应力纤维修复在细胞中微米级损伤位点的核心内开始，解释这些F-肌动蛋白耗尽区域是如何迅速恢复的。因此，肌动蛋白修复机制的zyxin力依赖性组织固有地在网络尺度上运行以维持细胞骨架的完整性。
