Molecular, Cellular and Developmental Biology Department, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Molecular, Cellular and Developmental Biology Department, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Dev Cell. 2022 Nov 7;57(21):2483-2496.e4. doi: 10.1016/j.devcel.2022.10.004.
Collective cell movements drive normal development and metastasis. Drosophila border cells move as a cluster of 6-10 cells, where the role of the Rac GTPase in migration was first established. In border cells, as in most migratory cells, Rac stimulates leading-edge protrusion. Upstream Rac regulators in leaders have been identified; however, the regulation and function of Rac in follower border cells is unknown. Here, we show that all border cells require Rac, which promotes follower-cell motility and is important for cluster compactness and movement. We identify a Rac guanine nucleotide exchange factor, Cdep, which also regulates follower-cell movement and cluster cohesion. Scribble, Discs large, and Lethal giant larvae localize Cdep basolaterally and share phenotypes with Cdep. Relocalization of Cdep::GFP partially rescues Scribble knockdown, suggesting that Cdep is a major downstream effector of basolateral proteins. Thus, a Scrib/Cdep/Rac pathway promotes cell crawling and coordinated, collective migration in vivo.
细胞集体运动驱动正常发育和转移。果蝇缘细胞作为一个由 6-10 个细胞组成的细胞簇运动，Rac GTPase 在迁移中的作用首先得到确立。在缘细胞中，与大多数迁移细胞一样，Rac 刺激前缘突起。已经鉴定出领导者中 Rac 的上游调节因子；然而，追随者缘细胞中 Rac 的调节和功能尚不清楚。在这里，我们表明所有的缘细胞都需要 Rac，Rac 促进了追随者细胞的运动，对于细胞簇的紧密性和运动至关重要。我们发现一种 Rac 鸟嘌呤核苷酸交换因子 Cdep，它也调节追随者细胞的运动和细胞簇的内聚性。Scribble、Discs large 和 Lethal giant larvae 将 Cdep 定位在基底外侧，并且与 Cdep 具有相同的表型。Cdep::GFP 的重定位部分挽救了 Scribble 敲低，这表明 Cdep 是基底外侧蛋白的主要下游效应物。因此，Scrib/Cdep/Rac 通路促进细胞爬行和体内协调的集体迁移。
