Cofilin-Linked Changes in Actin Filament Flexibility Promote Severing
Cofilin-Linked Changes in Actin Filament Flexibility Promote Severing
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DOI：
10.1016/j.bpj.2011.05.049
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发表时间：
2011-07-06
影响因子：
3.4
通讯作者：
De La Cruz, Enrique M.
中科院分区：
文献类型：
--
作者：
McCullough, Brannon R.;Grintsevich, Elena E.;De La Cruz, Enrique M.
肌动蛋白调节蛋白cofilin增加肌动蛋白丝的弯曲和扭转弹性，并切断它们。有人提出，用cofilin部分修饰的细丝在裸（刚性）和修饰（柔顺）边界处由于热驱动的形状波动而积累应力，从而促进了断裂。这种基于力学的切断模型预测，由于cofilin结合导致的肌动蛋白丝顺应性的变化会影响切断活性。在这里，我们通过评估脊椎动物和酵母协肌蛋白的切断活动如何与从形状波动分析确定的弯曲刚度的规模来验证这一预测。酵母肌动蛋白丝在弯曲时比脊椎动物肌动蛋白丝更柔顺。共丝肌动蛋白同工型的切断活性与纤维柔韧性的变化有关。脊椎动物的cofilin结合但不增加酵母肌动蛋白丝的柔韧性，也不切断它们。细丝热波动成像显示，当变形达到临界角时，切断事件与局部弯曲和碎裂有关。光丝和花丝之间的临界切断角小于光丝和花丝之间的临界切断角。这些测量结果支持了一种cofilin断裂机制，在这种机制中，机械不对称促进了裸段和cofilin修饰段边界的局部应力积累和断裂，类似于一些非蛋白材料的断裂。
The actin regulatory protein, cofilin, increases the bending and twisting elasticity of actin filaments and severs them. It has been proposed that filaments partially decorated with cofilin accumulate stress from thermally driven shape fluctuations at bare (stiff) and decorated (compliant) boundaries, thereby promoting severing. This mechanics-based severing model predicts that changes in actin filament compliance due to cofilin binding affect severing activity. Here, we test this prediction by evaluating how the severing activities of vertebrate and yeast cofilactin scale with the flexural rigidities determined from analysis of shape fluctuations. Yeast actin filaments are more compliant in bending than vertebrate actin filaments. Severing activities of cofilactin isoforms correlate with changes in filament flexibility. Vertebrate cofilin binds but does not increase the yeast actin filament flexibility, and does not sever them. Imaging of filament thermal fluctuations reveals that severing events are associated with local bending and fragmentation when deformations attain a critical angle. The critical severing angle at boundaries between bare and cofilin-decorated segments is smaller than in bare or fully decorated filaments. These measurements support a cofilin-severing mechanism in which mechanical asymmetry promotes local stress accumulation and fragmentation at boundaries of bare and cofilin-decorated segments, analogous to failure of some nonprotein materials.