Oosterheert Wout, Boiero Sanders Micaela, Bieling Peter, Raunser Stefan
Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany.
Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, 44227, Dortmund, Germany.
Trends Cell Biol. 2025 Jan 22. doi: 10.1016/j.tcb.2024.12.009.
The dynamic turnover of actin filaments drives the morphogenesis and migration of all eukaryotic cells. This review summarizes recent insights into the molecular mechanisms of actin polymerization and disassembly obtained through high-resolution structures of actin filament assemblies. We first describe how, upon polymerization, actin subunits age within the filament through changes in their associated adenine nucleotide. We then focus on the molecular basis of actin filament growth at the barbed end and how this process is modulated by core regulators such as profilin, formin, and capping protein (CP). Finally, the mechanisms underlying actin filament pointed-end depolymerization through disassembly factors cofilin/cyclase-associated protein (CAP) or DNase I are discussed. These findings contribute to a structural understanding of how actin filament dynamics are regulated in a complex cellular environment.
肌动蛋白丝的动态周转驱动着所有真核细胞的形态发生和迁移。本综述总结了通过肌动蛋白丝组装体的高分辨率结构获得的关于肌动蛋白聚合和解聚分子机制的最新见解。我们首先描述肌动蛋白亚基在聚合时如何通过其相关腺嘌呤核苷酸的变化在丝内老化。然后，我们将重点关注肌动蛋白丝在带刺末端生长的分子基础，以及这一过程如何受到诸如丝切蛋白、formin和封端蛋白（CP）等核心调节因子的调控。最后，讨论了通过解聚因子丝切蛋白/环化酶相关蛋白（CAP）或脱氧核糖核酸酶I实现肌动蛋白丝尖端解聚的潜在机制。这些发现有助于从结构上理解在复杂细胞环境中肌动蛋白丝动力学是如何被调控的。
