The WAVE complex associates with sites of saddle membrane curvature.

The WAVE complex associates with sites of saddle membrane curvature.
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DOI:
10.1083/jcb.202003086
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发表时间:
2021-08-02
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Weiner OD
Weiner OD
中科院分区:
其他
文献类型:
--
作者:
Pipathsouk A;Brunetti RM;Town JP;Graziano BR;Breuer A;Pellett PA;Marchuk K;Tran NT;Krummel MF;Stamou D;Weiner OD

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控制细胞形状和运动的局部规则还不清楚。在这里,Pipathsouk等人发现了一种新的关键肌动蛋白调节因子的纳米级组织,可以解释细胞突起如何扩展和自我拉直以及跨细胞孔如何修复。肌动蛋白调节子的局部相互作用如何产生细胞形状和运动的大规模组织尚不清楚。在这里,我们调查如何波复杂组织片状伪足。使用超分辨率显微镜,我们发现,波复杂的形式肌动蛋白独立的230 nm宽的环,本地化的鞍膜曲率的区域。这种富集模式可以解释几种紧急的细胞行为,如扩张和自我拉直板状伪足和内皮细胞识别和密封跨细胞孔的能力。WAVE复合体将IRSp 53募集到鞍形弯曲的位点,但不依赖于IRSp 53进行自身定位。尽管WAVE复合物通过Arp 2/3复合物刺激肌动蛋白成核,但在ARP 2-null细胞中仍然观察到片状突起,而不是WAVE复合物-null细胞。因此,WAVE复合物在Arp 2/3复合物激活之外的细胞形态发生中具有额外的作用。我们的工作定义了WAVE复合体板状伪足模板的组织原理,并提出了细胞形状和肌动蛋白调节因子之间的反馈如何指导细胞形态发生。
The local rules that control cell shape and movement are not understood. Here, Pipathsouk et al. discover a novel nanoscale organization of a key actin regulator that could explain how cellular protrusions expand and self-straighten and how transcellular holes are repaired. How local interactions of actin regulators yield large-scale organization of cell shape and movement is not well understood. Here we investigate how the WAVE complex organizes sheet-like lamellipodia. Using super-resolution microscopy, we find that the WAVE complex forms actin-independent 230-nm-wide rings that localize to regions of saddle membrane curvature. This pattern of enrichment could explain several emergent cell behaviors, such as expanding and self-straightening lamellipodia and the ability of endothelial cells to recognize and seal transcellular holes. The WAVE complex recruits IRSp53 to sites of saddle curvature but does not depend on IRSp53 for its own localization. Although the WAVE complex stimulates actin nucleation via the Arp2/3 complex, sheet-like protrusions are still observed in ARP2-null, but not WAVE complex-null, cells. Therefore, the WAVE complex has additional roles in cell morphogenesis beyond Arp2/3 complex activation. Our work defines organizing principles of the WAVE complex lamellipodial template and suggests how feedback between cell shape and actin regulators instructs cell morphogenesis.
肌动蛋白调节波复合物的结构和控制。
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