Coro1B and Coro1C regulate lamellipodia dynamics and cell motility by tuning branched actin turnover.

Coro1B and Coro1C regulate lamellipodia dynamics and cell motility by tuning branched actin turnover.
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DOI:
10.1083/jcb.202111126
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发表时间:
2022-08-01
影响因子:
7.8
通讯作者:
Bear, James E.
Bear, James E.
中科院分区:
生物学1区
文献类型:
--
作者:
King, Zayna T.;Butler, Mitchell T.;Hockenberry, Max A.;Subramanian, Bhagawat C.;Siesser, Priscila F.;Graham, David M.;Legant, Wesley R.;Bear, James E.

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一种新的冠状蛋白条件性敲除细胞系阐明了其在调节ADF/cofilin功能中的作用的重要功能细节。肌动蛋白丝动力学必须在细胞中精确控制,以执行诸如囊泡运输、胞质分裂和迁移的行为。冠蛋白是一种保守的肌动蛋白结合蛋白,调节多种肌动蛋白依赖的亚细胞过程。在这里,我们描述了一个新的条件性敲除细胞系的两个普遍存在的冠状蛋白,Coro 1B和Coro 1C。这些冠状蛋白,强烈的共定位与Arp 2/3分支的肌动蛋白,需要Arp 2/3的活动,适当的亚细胞定位。冠状空细胞改变了板状伪足突起的动力学,由于增加分支肌动蛋白密度和减少肌动蛋白营业额内板状伪足,导致有缺陷的haptotaxis。令人惊讶的是,过多的cofilin积累在冠蛋白空板状伪足,结果是与冠蛋白-cofilin功能相互作用的当前模型不一致。然而,与冠状蛋白发挥原切丝蛋白作用一致,冠状蛋白空细胞具有增加的F-肌动蛋白水平。最后,我们证明了冠蛋白的损失增加伴随着细胞收缩性的增加。总之,我们的观察结果表明,冠状蛋白是至关重要的分支肌动蛋白网络的适当营业额和减少肌动蛋白营业额导致细胞收缩性增加。
A new conditional knockout cell line for coronins clarifies important functional details about its role in regulating ADF/cofilin function. 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.
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