Laboratoire Physico-Chimie Curie, Institut Curie, PSL Research University, CNRS, 75005 Paris, France.
Université Paris Descartes, 75005 Paris, France.
Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):11537-11542. doi: 10.1073/pnas.1808760115. Epub 2018 Oct 22.
During invasion, cells breach basement membrane (BM) barriers with actin-rich protrusions. It remains unclear, however, whether actin polymerization applies pushing forces to help break through BM, or whether actin filaments play a passive role as scaffolding for targeting invasive machinery. Here, using the developmental event of anchor cell (AC) invasion in , we observe that the AC deforms the BM and underlying tissue just before invasion, exerting forces in the tens of nanonewtons range. Deformation is driven by actin polymerization nucleated by the Arp2/3 complex and its activators, whereas formins and cross-linkers are dispensable. Delays in invasion upon actin regulator loss are not caused by defects in AC polarity, trafficking, or secretion, as appropriate markers are correctly localized in the AC even when actin is reduced and invasion is disrupted. Overall force production emerges from this study as one of the main tools that invading cells use to promote BM disruption in .
在入侵过程中,细胞利用富含肌动蛋白的突起突破基底膜(BM)的屏障。然而,目前尚不清楚肌动蛋白聚合是否会产生推挤力来帮助突破 BM,还是肌动蛋白丝作为靶向入侵机制的支架发挥被动作用。在这里,我们利用 中的锚定细胞(AC)入侵的发育事件观察到,AC 在入侵前会对 BM 和下方组织进行变形,施加的力在数十纳牛顿的范围内。变形是由 Arp2/3 复合物及其激活剂引发的肌动蛋白聚合驱动的,而formin 和交联剂则是可有可无的。肌动蛋白调节剂缺失导致入侵延迟并不是由于 AC 极性、运输或分泌缺陷引起的,因为适当的标记物即使在肌动蛋白减少和入侵受阻时仍能正确定位于 AC 中。总的来说,这项研究表明,力的产生是入侵细胞用来促进 的 BM 破坏的主要工具之一。