Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
J Cell Biol. 2012 Apr 16;197(2):239-51. doi: 10.1083/jcb.201112113. Epub 2012 Apr 9.
The Arp2/3 complex nucleates the formation of the dendritic actin network at the leading edge of motile cells, but it is still unclear if the Arp2/3 complex plays a critical role in lamellipodia protrusion and cell motility. Here, we differentiated motile fibroblast cells from isogenic mouse embryonic stem cells with or without disruption of the ARPC3 gene, which encodes the p21 subunit of the Arp2/3 complex. ARPC3(-/-) fibroblasts were unable to extend lamellipodia but generated dynamic leading edges composed primarily of filopodia-like protrusions, with formin proteins (mDia1 and mDia2) concentrated near their tips. The speed of cell migration, as well as the rates of leading edge protrusion and retraction, were comparable between genotypes; however, ARPC3(-/-) cells exhibited a strong defect in persistent directional migration. This deficiency correlated with a lack of coordination of the protrusive activities at the leading edge of ARPC3(-/-) fibroblasts. These results provide insights into the Arp2/3 complex's critical role in lamellipodia extension and directional fibroblast migration.
Arp2/3 复合物在运动细胞的前缘引发树突状肌动蛋白网络的形成，但尚不清楚 Arp2/3 复合物是否在片状伪足的伸出和细胞运动中发挥关键作用。在这里，我们从同基因的小鼠胚胎干细胞中分化出具有或不破坏编码 Arp2/3 复合物的 p21 亚基的 ARPC3 基因的运动成纤维细胞。ARPC3(-/-)成纤维细胞无法伸出片状伪足，但形成主要由丝状伪足样突起组成的动态前缘，formin 蛋白（mDia1 和 mDia2）集中在其尖端附近。细胞迁移的速度以及前缘的伸出和缩回的速度在基因型之间相当；然而，ARPC3(-/-)细胞在持续的定向迁移中表现出严重的缺陷。这种缺陷与 ARPC3(-/-)成纤维细胞前缘的突出活动缺乏协调性有关。这些结果为 Arp2/3 复合物在片状伪足延伸和定向成纤维细胞迁移中的关键作用提供了深入了解。
