ATP hydrolysis on actin-related protein 2/3 complex causes debranching of dendritic actin arrays
ATP hydrolysis on actin-related protein 2/3 complex causes debranching of dendritic actin arrays
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DOI：
10.1073/pnas.1130513100
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发表时间：
2003-05-27
影响因子：
11.1
通讯作者：
Carlier, MF
中科院分区：
文献类型：
--
作者：
Le Clainche, C;Pantaloni, D;Carlier, MF
片状伪足的延伸是细胞运动中的一个重要耗散过程，它是由极化的树突状肌动蛋白丝阵列的翻转驱动的。运动性是由丝状体附着于Wiskott-Aldrich综合征蛋白（WASP）激活的肌动蛋白相关蛋白（阿普）2/3复合物前缘、分支形成和分离的催化循环驱动的，从而允许分支丝状体的后续生长。阵列的形态、机械强度和寿命由长丝支化、去支化和微粉碎的过程决定。这三个过程都是由ATP水解控制的。已知ATP在F-肌动蛋白上的水解作用是螺旋碾磨的起源。在这里，通过使用放射性标记的ATP共价结合到Arp 2/3，我们表明，ATP水解Arp 2，而不是Arp 3，延迟后丝分支。水解ATP的Arp 2促进纤维的脱支，并作为一个时钟，控制树突状肌动蛋白阵列的稳定性在板状伪足。最后，我们提出，水解ATP对G-肌动蛋白的三元G-actin-WASP-Arp 2/3复合物的分支形成不稳定的WASP-肌动蛋白接口，大力促进分支反应中的分离步骤。
Extension of lamellipodia, an important dissipative process in cell motility, is driven by the turnover of a polarized dendritic array of actin filaments. Motility is driven by catalytic cycles of filament attachment to Wiskott-Aldrich syndrome protein (WASP)-activated actin-related protein (Arp)2/3 complex at the leading edge, branch formation, and detachment, allowing subsequent growth of branched filaments. The morphology, mechanical strength, and lifetime of the array are determined by the processes of filament branching, debranching, and treadmilling. All three processes are controlled by ATP hydrolysis. ATP hydrolysis on F-actin is known to be at the origin of treadmilling. Here, by using radiolabeled ATP covalently bound to Arp2/3, we show that ATP is hydrolyzed on Arp2, not on Arp3, after a delay following filament branching. Hydrolysis of ATP on Arp2 promotes debranching of filaments and acts as a clock that controls the stability of dendritic actin arrays in lamellipodia. Finally, we propose that hydrolysis of ATP on G-actin in the ternary G-actin-WASP-Arp2/3 complex on branch formation destabilizes the WASP-actin interface and energetically facilitates the detachment step in the branching reaction.