Septins promote stress fiber-mediated maturation of focal adhesions and renal epithelial motility
Septins promote stress fiber-mediated maturation of focal adhesions and renal epithelial motility
复制标题
DOI：
10.1083/jcb.201405050
复制
发表时间：
2014-10-27
影响因子：
7.8
通讯作者：
Spiliotis, Elias T.
中科院分区：
文献类型：
--
作者：
Dolat, Lee;Hunyara, John L.;Spiliotis, Elias T.
器官发生和肿瘤转移涉及上皮细胞向高运动性间充质样细胞的转化。Septins是一种丝状G蛋白，在转移性癌中过度表达，但其在上皮运动中的功能尚不清楚。在这里，我们显示了一种新的隔膜细丝网络，位于迁移的肾上皮细胞的前导板的横弧和径向(背部)应力纤维的组织之下。令人惊讶的是，间隔蛋白的缺失导致了更小、更短暂的周围局灶性粘连。这种表型伴随着高度紊乱的板层肌动蛋白网络，并被肌动蛋白捆绑蛋白α-肌动蛋白-1拯救。我们发现，预先组装的肌动蛋白细丝直接被Septin 9(SEPT9)交联，在肝细胞生长因子诱导肾上皮运动后，SEPT9的表达增加。值得注意的是，SEPT9过表达促进了2D和3D基质中的肾细胞迁移，而SEPT9基因敲除则减少了迁移。这些结果表明，Septins通过加强板层应力纤维的交联性和新生灶性粘连的稳定性来促进上皮的运动。
Organogenesis and tumor metastasis involve the transformation of epithelia to highly motile mesenchymal-like cells. Septins are filamentous G proteins, which are overexpressed in metastatic carcinomas, but their functions in epithelial motility are unknown. Here, we show that a novel network of septin filaments underlies the organization of the transverse arc and radial (dorsal) stress fibers at the leading lamella of migrating renal epithelia. Surprisingly, septin depletion resulted in smaller and more transient and peripheral focal adhesions. This phenotype was accompanied by a highly disorganized lamellar actin network and rescued by the actin bundling protein a-actinin-1. We show that preassembled actin filaments are cross-linked directly by Septin 9 (SEPT9), whose expression is increased after induction of renal epithelial motility with the hepatocyte growth factor. Significantly, SEPT9 overexpression enhanced renal cell migration in 2D and 3D matrices, whereas SEPT9 knockdown decreased migration. These results suggest that septins promote epithelial motility by reinforcing the cross-linking of lamellar stress fibers and the stability of nascent focal adhesions