Competition and Synergy of Arp2/3 and Formins in Nucleating Actin Waves.
Competition and Synergy of Arp2/3 and Formins in Nucleating Actin Waves.
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Arp2/3 和 Formins 在成核肌动蛋白波中的竞争和协同作用。
DOI：
10.1101/2023.09.13.557508
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Wu,Min
中科院分区：
文献类型：
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作者：
LeChua,Xiang;Tong,CheeSan;Xǔ,XJ;Su,Maohan;Xiao,Shengping;Wu,Xudong;Wu,Min
肌动蛋白组装和动力学对于维持细胞结构和改变生理状态至关重要。肌动蛋白对各种细胞过程的广泛影响使得剖析肌动蛋白调节蛋白的特定作用具有挑战性。使用肌动蛋白波作为模型的肥大细胞的皮质上传播，我们发现，formins（FMNL 1和mDia 3）之前招募的Arp 2/3复合物的肌动蛋白波。GT3 Cdc 42相互作用驱动FMNL 1振荡，具有活性Cdc 42和FMNL 1的组成型活性突变体能够独立于肌动蛋白波在质膜上形成波。此外，Arp 2/3的延迟募集拮抗FMNL 1和活性Cdc 42。这种拮抗作用不是由于单体肌动蛋白的竞争，而是由于它们共同的上游调节因子活性Cdc 42的竞争，其水平通过SHIP 1募集由Arp 2/3负调控。总的来说，我们的研究突出了肌动蛋白细胞骨架网络动态控制中的复杂反馈回路。
Actin assembly and dynamics are crucial for maintaining cell structure and changing physiological states. The broad impact of actin on various cellular processes makes it challenging to dissect the specific role of actin regulatory proteins. Using actin waves that propagate on the cortex of mast cells as a model, we discovered that formins (FMNL1 and mDia3) are recruited before the Arp2/3 complex in actin waves. GTPase Cdc42 interactions drive FMNL1 oscillations, with active Cdc42 and the constitutively active mutant of FMNL1 capable of forming waves on the plasma membrane independently of actin waves. Additionally, the delayed recruitment of Arp2/3 antagonizes FMNL1 and active Cdc42. This antagonism is not due to competition for monomeric actin but rather for their common upstream regulator, active Cdc42, whose levels are negatively regulated by Arp2/3 via SHIP1 recruitment. Collectively, our study highlights the complex feedback loops in the dynamic control of the actin cytoskeletal network.