Zigmond Sally H
Biology Department, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Curr Top Dev Biol. 2004;63:145-88. doi: 10.1016/S0070-2153(04)63005-5.
Dynamic actin filaments contribute to cell migration, organelle movements, memory, and gene regulation. These dynamic processes are often regulated by extracellular and?or cell cycle signals. Regulation targets, not actin itself, but the factors that determine it's dynamic properties. Thus, filament nucleation, rate and duration of elongation, and depolymerization are each controlled with regard to time and?or space. Two mechanisms exist for nucleating filaments de novo, the Arp23 complex and the formins; multiple pathways regulate each. A new filament elongates rapidly but transiently before its barbed end is capped. Rapid capping allows the cell to maintain fine temporal and spatial control over F-actin distribution. Modulation of capping protein activity and its access to barbed ends is emerging as a site of local regulation. Finally, to maintain a steady state filaments must depolymerize. Depolymerization can limit the rate of new filament nucleation and elongation. The activity of ADF?cofilin, which facilitates depolymerization, is also regulated by multiple inputs. This chapter describes (1) mechanism and regulation of new filament formation, (2) mechanism of enhancing elongation at barbed ends, (3) capping proteins and their regulators, and (4) recycling of actin monomers from filamentous actin (F-actin) back to globular actin (G-actin).
动态肌动蛋白丝参与细胞迁移、细胞器运动、记忆和基因调控。这些动态过程通常受细胞外和/或细胞周期信号调控。调控的目标并非肌动蛋白本身，而是决定其动态特性的因素。因此，丝的成核、伸长速率和持续时间以及解聚在时间和/或空间上均受到控制。存在两种从头形成丝的机制，即Arp23复合体和formin；每种机制都有多种调控途径。新形成的丝在其带刺末端被封闭之前会迅速但短暂地伸长。快速封闭使细胞能够对F-肌动蛋白分布进行精细的时空控制。帽蛋白活性及其与带刺末端结合的调控正成为局部调控的一个位点。最后，为维持稳态，丝必须解聚。解聚可限制新丝成核和伸长的速率。促进解聚的ADF-丝切蛋白的活性也受多种因素调控。本章描述了（1）新丝形成的机制和调控，（2）带刺末端伸长增强的机制，（3）帽蛋白及其调控因子，以及（4）肌动蛋白单体从丝状肌动蛋白（F-肌动蛋白）循环回到球状肌动蛋白（G-肌动蛋白）的过程。
