Competitive displacement of cofilin can promote actin filament severing.
Competitive displacement of cofilin can promote actin filament severing.
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DOI：
10.1016/j.bbrc.2013.07.109
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发表时间：
2013-09-06
影响因子：
3.1
通讯作者：
De La Cruz EM
中科院分区：
文献类型：
--
作者：
Elam WA;Kang H;De La Cruz EM
Cofilin是一种重要的肌动蛋白丝切割蛋白，在肌动蛋白细胞骨架的动态重塑中发挥作用。丝切断活性在亚化学计量的丝切蛋白结合密度（即每个肌动蛋白丝亚基<1个丝切蛋白）下最有效，并且当裸片段和丝切蛋白修饰片段之间的边界（即连接）的数量密度最大时达到峰值。一个模型，其中局部拓扑和机械的不连续性导致优先破碎的边界占现有的实验数据，包括直接可视化的cofilin和肌动蛋白在实时切断事件。边界切断模型预测，与cofilin竞争肌动蛋白丝结合并调节cofilin在丝上占据的配体（例如，其他肌动蛋白结合蛋白）将改变裸装饰片段边界密度，从而改变cofilin的丝切断活性。在这里，我们直接测试这个模型的预测，通过评估鬼笔环肽和肌球蛋白，两个配体，竞争与丝切蛋白的细丝结合，对肌动蛋白丝的结合和切断活动的丝切蛋白的影响。我们的实验表明，当初始的丝切蛋白占据率高（即>50%）时，丝切蛋白的竞争性置换降低了丝切蛋白占据率并促进切断。即使在竞争性配体的存在下，最大切断活性发生时，cofilin装饰的边界密度是最高的，在边界处的优先碎片一致。我们提出了一个一般的“severodyne”框架的调制cofilin介导的肌动蛋白丝切断小分子或肌动蛋白结合蛋白配体，竞争与cofilin肌动蛋白丝结合。
Cofilin is an essential actin filament severing protein that functions in the dynamic remodeling of the actin cytoskeleton. Filament severing activity is most efficient at sub-stoichiometric cofilin binding densities (i.e. <1 cofilin per actin filament subunit), and peaks when the number density of boundaries (i.e. junctions) between bare and cofilin-decorated segments is maximal. A model in which local topological and mechanical discontinuities lead to preferential fragmentation at boundaries accounts for available experimental data, including direct visualization of cofilin and actin during real-time severing events. The boundary-severing model predicts that ligands (e.g. other actin-binding proteins) that compete with cofilin for actin filament binding and modulate cofilin occupancy on filaments will alter the bare-decorated segment boundary density, and thus, the filament severing activity of cofilin. Here, we directly test this model prediction by evaluating the effects of phalloidin and myosin, two ligands that compete with cofilin for filament binding, on the actin filament binding and severing activities of cofilin. Our experiments demonstrate that competitive displacement of cofilin lowers cofilin occupancy and promotes severing when initial cofilin occupancy is high (i.e. >50%). Even in the presence of competitive ligands, maximum severing activity occurs when cofilin-decorated boundary density is highest, consistent with preferential fragmentation at boundaries. We propose a general “severodyne” framework for the modulation of cofilin-mediated actin filament severing by small molecule or actin-binding protein ligands that compete with cofilin for actin filament binding.
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影响因子：
16
作者：
Andrianantoandro, Ernesto;Pollard, Thomas D.
通讯作者：
Pollard, Thomas D.
影响因子：
4.8
作者：
Okada, K;Blanchoin, L;Bamburg, JR
通讯作者：
Bamburg, JR
影响因子：
2.9
作者：
EDELHOCH, H
通讯作者：
EDELHOCH, H
影响因子：
64.8
作者：
Holmes, KC;Angert, I;Schröder, RR
通讯作者：
Schröder, RR
DOI：
10.1073/pnas.1211078109
发表时间：
2012-10-16
影响因子：
11.1
作者：
Kang, Hyeran;Bradley, Michael J.;De La Cruz, Enrique M.
通讯作者：
De La Cruz, Enrique M.