Actin bends over backward for directional branching.
Actin bends over backward for directional branching.
复制标题
肌动蛋白向后弯曲以进行定向分支。
DOI：
10.1073/pnas.1121360109
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发表时间：
2012
影响因子：
11.1
通讯作者：
Svitkina,TatyanaM
中科院分区：
文献类型：
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作者：
Svitkina,TatyanaM
肌动蛋白细胞骨架是细胞中主要的力产生机制，产生推力、拉力和阻力。为了执行这些功能，肌动蛋白丝在许多辅助蛋白的帮助下，形成专为特定目的而设计的结构独特的结构。因此，推力通常由分支网络产生，分支网络在负载附近聚集并利用肌动蛋白聚合的能量施加力 (1, 2)。尽管目前对该过程的分子和生物物理学理解水平堪称典范 (3, 4)，但剩下的一个关键问题是如何保持不断分支网络的方向性并防止其扩展到不需要的细胞区域。 Risca 等人的报告。在 PNAS (5) 中，将肌动蛋白分支的方向性与肌动蛋白丝的负载施加曲率联系起来。这种连接支持肌动蛋白丝的直接机械传感作用，并解释了肌动蛋白聚合向负载的隧道效应。负责组装分支肌动蛋白网络的分子机器由少数蛋白质组成，这些蛋白质足以从纯化的成分在体外重建运动性 (6)。该机制的一个关键组成部分是 Arp2/3 复合体，这是一种异七聚体蛋白质，它以 70 度的特定角度在预先存在的“母”细丝一侧成核新的“子”细丝作为分支，这一过程称为“树突成核”。经过一段时间的伸长后，与肌动蛋白丝生长的“带刺”末端结合的加帽蛋白会终止分支的生长，并且新的丝由 Arp2/3 复合物成核以维持力的产生 (2)。树突成核机制在产生推力方面具有许多优势，解释了其广泛的细胞功能，包括迁移细胞中板状伪足的突出、膜细胞器和细胞内病原体的火箭运动、细胞-细胞连接和突触的形成以及各种细胞内细胞器的生物发生 (1)。事实上，固定在母细丝上可以让子细丝在出生后立即做有用的工作，而不是在没有牵引力的情况下向后滑动。此外，这些新生的分支在它们仍然相对较短和僵硬的同时就产生了力量，而较长且生产力较低的细丝则被覆盖。推动肌动蛋白丝的倾斜方向
The actin cytoskeleton is the major force-generating machinery in the cell that produces pushing, pulling, and resistance forces. To perform these functions, actin filaments, with the help of many accessory proteins, form architecturally distinct structures designed for specific purposes. Thus, pushing forces are frequently generated by branched networks that assemble in the vicinity of a load and exert force using energy of actin polymerization (1, 2). Although the current level of molecular and biophysical understanding of this process is exemplary (3, 4), a key remaining question is how to maintain the directionality of the constantly branching network and prevent it from expanding into unwanted cell areas. The report by Risca et al. in PNAS (5) links the directionality of actin branching to the loadimposed curvature of actin filaments. This connection supports a direct mechanosensing role of actin filaments and explains the tunneling of actin polymerization toward the load.The molecular machinery responsible for the assembly of branched actin networks consists of a handful of proteins that were sufficient to reconstitute motility in vitro from purified components (6). A key component of the machinery is the Arp2/3 complex, a heteroheptameric protein that nucleates a new “daughter” filament as a branch on the side of a preexisting “mother” filament at a defined angle of 70, a process called “dendritic nucleation.” After a period of elongation, growth of branches is terminated by capping proteins that bind to the growing “barbed” ends of actin filaments, and new filaments are nucleated by the Arp2/3 complex to maintain force generation (2). The dendritic nucleation machinery has many advantages for pushing force generation, explaining its broad repertoire of cellular functions that includes protrusion of lamellipodia in migrating cells, rocketing motility of membrane organelles and intracellular pathogens, formation of cell–cell junctions and synapses, and biogenesis of various intracellular organelles (1). Indeed, anchorage to mother filaments allows daughter filaments to do useful work immediately after birth instead of slipping backward in the absence of traction. Moreover, these nascent branches produce force while they are still relatively short and stiff, whereas longer and less productive filaments are capped. An angled orientation of pushing actin fila-