Actin-filament stochastic dynamics mediated by ADF/cofilin
Actin-filament stochastic dynamics mediated by ADF/cofilin
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DOI：
10.1016/j.cub.2007.04.037
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发表时间：
2007-05-15
期刊：
影响因子：
9.2
通讯作者：
Blanchoin, Laurent
中科院分区：
文献类型：
--
作者：
Michelot, Alphee;Berro, Julien;Blanchoin, Laurent
背景：肌动蛋白丝的快速动力学是一个基本的过程，为大量的细胞功能提供动力。然而，控制和协调这种动力学的基本机制仍然是细胞生物学的核心问题。为了超越简单地定义控制肌动蛋白动力学的分子的库存，并了解这些蛋白质如何协同作用，以调节丝营业额，我们结合了倏逝波显微镜与仿生系统，并遵循在存在的生理相关的辅助蛋白质的混合物的单个肌动蛋白丝的行为。这种方法允许实时可视化的肌动蛋白聚合和年龄相关的丝severing.Results：在肌动蛋白解聚因子（ADF）/cofilin和profilin的存在下，肌动蛋白丝与一个进行性的连接在其倒刺的末端观察到随机增长和收缩阶段之间的振荡。ADF/cofilin对连续生长的肌动蛋白丝的断裂是调节显著和频繁的缩短事件的关键机制。连续肌动蛋白聚合的净效应，驱动的一个进行性的切割，使用profilin-actin，和ADF/cofilin介导切断，修剪老化的末端的生长丝是一个高达155倍的增加，在体外的肌动蛋白丝周转率相比，单独的肌动蛋白。肌动蛋白丝之间的横向接触抑制了动力学，有利于肌动蛋白电缆的形成。动力学模拟准确地验证了这些observation.Conclusions：我们提出的肌动蛋白动力学的控制机制是占主导地位的ADF/cofilin介导的丝切断，诱导个体肌动蛋白丝的随机行为。当结合选择过程，稳定纤维束，这种机制可以解释的肌动蛋白为基础的结构在细胞中的出现和扩展。
Background: The rapid dynamics of actin filaments is a fundamental process that powers a large number of cellular functions. However, the basic mechanisms that control and coordinate such dynamics remain a central question in cell biology. To reach beyond simply defining the inventory of molecules that control actin dynamics and to understand how these proteins act synergistically to modulate filament turnover, we combined evanescent-wave microscopy with a biomimetic system and followed the behavior of single actin filaments in the presence of a physiologically relevant mixture of accessory proteins. This approach allows for the real-time visualization of actin polymerization and age-dependent filament severing.Results: In the presence of actin-depolymerizing factor (ADF)/cofilin and profilin, actin filaments with a processive formin attached at their barbed ends were observed to oscillate between stochastic growth and shrinkage phases. Fragmentation of continuously growing actin filaments by ADF/cofilin is the key mechanism modulating the prominent and frequent shortening events. The net effect of continuous actin polymerization, driven by a processive formin that uses profilin-actin, and of ADF/cofilin-mediating severing that trims the aged ends of the growing filaments is an up to 155-fold increase in the rate of actin-filament turnover in vitro in comparison to that of actin alone. Lateral contact between actin filaments dampens the dynamics and favors actin-cable formation. A kinetic simulation accurately validates these observations.Conclusions: Our proposed mechanism for the control of actin dynamics is dominated by ADF/cofilin-mediated filament severing that induces a stochastic behavior upon individual actin filaments. When combined with a selection process that stabilizes filaments in bundles, this mechanism could account for the emergence and extension of actin-based structures in cells.