Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, Santa Barbara, CA.
J Cell Biol. 2022 Jul 4;221(7). doi: 10.1083/jcb.202202146. Epub 2022 May 25.
Border cells are an in vivo model for collective cell migration. Here, we identify the gene cactin as essential for border cell cluster organization, delamination, and migration. In Cactin-depleted cells, the apical proteins aPKC and Crumbs (Crb) become abnormally concentrated, and overall cluster polarity is lost. Apically tethering excess aPKC is sufficient to cause delamination defects, and relocalizing apical aPKC partially rescues delamination. Cactin is conserved from yeast to humans and has been implicated in diverse processes. In border cells, Cactin's evolutionarily conserved spliceosome function is required. Whole transcriptome analysis revealed alterations in isoform expression in Cactin-depleted cells. Mutations in two affected genes, Sec23 and Sec24CD, which traffic Crb to the apical cell surface, partially rescue border cell cluster organization and migration. Overexpression of Rab5 or Rab11, which promote Crb and aPKC recycling, similarly rescues. Thus, a general splicing factor is specifically required for coordination of cluster polarity and migration, and migrating border cells are particularly sensitive to splicing and cell polarity disruptions.
边缘细胞是一种用于细胞集体迁移的活体模型。在这里，我们确定基因 cactin 对于边缘细胞簇的组织、分离和迁移是必不可少的。在 Cactin 耗尽的细胞中，顶端蛋白 aPKC 和 Crumbs（Crb）变得异常集中，并且整体簇极性丧失。过度锚定顶端的 aPKC 足以导致分离缺陷，并且重新定位顶端的 aPKC 部分挽救了分离。Cactin 从酵母到人类都是保守的，并且已经涉及到多种过程。在边缘细胞中，Cactin 的进化保守剪接体功能是必需的。全转录组分析显示，Cactin 耗尽的细胞中存在同工型表达的改变。Sec23 和 Sec24CD 这两个受影响基因的突变，它们将 Crb 运送到顶端细胞表面，部分挽救了边缘细胞簇的组织和迁移。Rab5 或 Rab11 的过表达，它们促进 Crb 和 aPKC 的再循环，也有类似的挽救作用。因此，一般的剪接因子对于协调簇极性和迁移是特异性需要的，并且正在迁移的边缘细胞对剪接和细胞极性破坏特别敏感。
