Actin filament dynamics must be precisely controlled in cells to execute behaviors such as vesicular trafficking, cytokinesis, and migration. Coronins are conserved actin-binding proteins that regulate several actin-dependent subcellular processes. Here, we describe a new conditional knockout cell line for two ubiquitous coronins, Coro1B and Coro1C. These coronins, which strongly co-localize with Arp2/3-branched actin, require Arp2/3 activity for proper subcellular localization. Coronin null cells have altered lamellipodial protrusion dynamics due to increased branched actin density and reduced actin turnover within lamellipodia, leading to defective haptotaxis. Surprisingly, excessive cofilin accumulates in coronin null lamellipodia, a result that is inconsistent with the current models of coronin–cofilin functional interaction. However, consistent with coronins playing a pro-cofilin role, coronin null cells have increased F-actin levels. Lastly, we demonstrate that the loss of coronins increases accompanied by an increase in cellular contractility. Together, our observations reveal that coronins are critical for proper turnover of branched actin networks and that decreased actin turnover leads to increased cellular contractility.

中文翻译：

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Coro1B 和 Coro1C 通过调节分支肌动蛋白周转来调节片状伪足动力学和细胞运动

细胞中的肌动蛋白丝动力学必须受到精确控制才能执行囊泡运输、胞质分裂和迁移等行为。 Coronins 是保守的肌动蛋白结合蛋白，可调节多种肌动蛋白依赖性亚细胞过程。在这里，我们描述了两种普遍存在的 Coronins Coro1B 和 Coro1C 的新条件敲除细胞系。这些冠蛋白与 Arp2/3 分支肌动蛋白强烈共定位，需要 Arp2/3 活性才能实现正确的亚细胞定位。由于片状伪足内分支肌动蛋白密度增加和肌动蛋白周转减少，Coronin 无效细胞改变了片状伪足突出动力学，导致趋触性缺陷。令人惊讶的是，过量的cofilin在coronin无效板状伪足中积累，这一结果与当前的coronin-cofilin功能相互作用模型不一致。然而，与 Coronins 发挥原丝切蛋白作用一致，Coronin 无效细胞的 F-肌动蛋白水平增加。最后，我们证明冠蛋白的损失随着细胞收缩力的增加而增加。总之，我们的观察结果表明，冠蛋白对于分支肌动蛋白网络的正常周转至关重要，并且肌动蛋白周转减少会导致细胞收缩性增加。