Division of Developmental Biology, Institute of Biodynamics and Biocomplexity, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
PLoS Genet. 2021 Oct 21;17(10):e1009856. doi: 10.1371/journal.pgen.1009856. eCollection 2021 Oct.
The conserved adapter protein Scribble (Scrib) plays essential roles in a variety of cellular processes, including polarity establishment, proliferation, and directed cell migration. While the mechanisms through which Scrib promotes epithelial polarity are beginning to be unraveled, its roles in other cellular processes including cell migration remain enigmatic. In C. elegans, the Scrib ortholog LET-413 is essential for apical-basal polarization and junction formation in embryonic epithelia. However, whether LET-413 is required for postembryonic development or plays a role in migratory events is not known. Here, we use inducible protein degradation to investigate the functioning of LET-413 in larval epithelia. We find that LET-413 is essential in the epidermal epithelium for growth, viability, and junction maintenance. In addition, we identify a novel role for LET-413 in the polarized outgrowth of the epidermal seam cells. These stem cell-like epithelial cells extend anterior and posterior directed apical protrusions in each larval stage to reconnect to their neighbors. We show that the role of LET-413 in seam cell outgrowth is likely mediated largely by the junctional component DLG-1 discs large, which we demonstrate is also essential for directed outgrowth of the seam cells. Our data uncover multiple essential functions for LET-413 in larval development and show that the polarized outgrowth of the epithelial seam cells is controlled by LET-413 Scribble and DLG-1 Discs large.
保守的衔接蛋白 Scribble(Scrib)在多种细胞过程中发挥着重要作用,包括极性建立、增殖和定向细胞迁移。虽然 Scrib 促进上皮极性的机制开始被揭示,但它在包括细胞迁移在内的其他细胞过程中的作用仍然是个谜。在秀丽隐杆线虫中,Scrib 同源物 LET-413 对于胚胎上皮的顶底极性和连接形成是必需的。然而,LET-413 是否在胚胎后发育中是必需的,或者是否在迁移事件中发挥作用,目前尚不清楚。在这里,我们使用诱导蛋白降解来研究 LET-413 在幼虫上皮细胞中的功能。我们发现 LET-413 在表皮上皮细胞的生长、存活和连接维持中是必需的。此外,我们发现 LET-413 在表皮 seam 细胞的极化生长中具有新的作用。这些干细胞样上皮细胞在每个幼虫阶段向前和向后延伸定向的顶端突起,以重新连接到它们的邻居。我们表明,LET-413 在 seam 细胞生长中的作用可能主要是通过连接蛋白 DLG-1(Discs large)介导的,我们证明 DLG-1 对于 seam 细胞的定向生长也是必需的。我们的数据揭示了 LET-413 在幼虫发育中的多个必需功能,并表明上皮 seam 细胞的极化生长受 LET-413 Scribble 和 DLG-1 Discs large 的控制。