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The Arp2/3 inhibitory protein arpin induces cell turning by pausing cell migration

机译:Arp2 / 3抑制蛋白arpin通过暂停细胞迁移诱导细胞转向

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Branched actin networks generated by the Arp2/3 complex provide the driving force for leading edge protrusion in migrating cells. We recently identified Arpin, a protein that inhibits the Arp2/3 complex in lamellipodia. Arpin is activated by the small GTPase Rac, which triggers lamellipodium formation, and thus Arpin renders protrusions unstable. A conserved role of Arpin is to induce migrating cells to turn in different migration models. Here we investigated the mechanism by which Arpin controls directional persistence. For this analysis, we segmented migration trajectories into alternating phases of active migration and pauses, based on a speed threshold. Regardless of the threshold value, Arpin induced more frequent pausing, during which the cell was more likely to change the direction of its migration. Arpin simultaneously acts on cell speed and directional persistence, which are strongly coupled parameters. Induction of frequent pausing by Arpin is consistent with Arpin circuitry: by inhibiting the Arp2/3 complex as a response to Rac activation, Arpin antagonizes a positive feedback loop that sustains protrusions at the leading edge and maintains active migration. We propose the duration of active migration' as a useful proxy to measure feedbacks associated with cell migration. (c) 2015 Wiley Periodicals, Inc.
机译:由Arp2 / 3复合物生成的分支肌动蛋白网络为迁移细胞中的前缘突出提供了驱动力。我们最近确定了Arpin,一种抑制片状脂蛋白中Arp2 / 3复合物的蛋白。 Arpin被小的GTPase Rac激活,从而触发层状脂蛋白的形成,因此Arpin使突起变得不稳定。 Arpin的保守作用是诱导迁移细胞转变为不同的迁移模型。在这里,我们研究了Arpin控制方向持久性的机制。对于此分析,我们基于速度阈值将迁移轨迹划分为活动迁移和暂停的交替阶段。无论阈值如何,Arpin都会引起更频繁的暂停,在此期间,细胞更可能会改变其迁移方向。 Arpin同时作用于细胞速度和方向持久性,这是强烈耦合的参数。 Arpin引起的频繁暂停与Arpin电路一致:通过抑制Arp2 / 3复合体作为对Rac激活的响应,Arpin拮抗了一个正反馈环,该环维持了前沿的突出并维持了活跃的迁移。我们提出“主动迁移的持续时间”作为衡量与细胞迁移相关的反馈的有用代理。 (c)2015年威利期刊有限公司

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