Global Centers of Excellence Program for Integrative Membrane Biology, Graduate School of Medicine, Kobe University, Chuo-ku, Kobe 650-0017, Japan.
J Cell Biol. 2011 Oct 17;195(2):245-61. doi: 10.1083/jcb.201104118.
Myosin II-driven mechanical forces control epithelial cell shape and morphogenesis. In particular, the circumferential actomyosin belt, which is located along apical cell-cell junctions, regulates many cellular processes. Despite its importance, the molecular mechanisms regulating the belt are not fully understood. In this paper, we characterize Lulu2, a FERM (4.1 protein, ezrin, radixin, moesin) domain-containing molecule homologous to Drosophila melanogaster Yurt, as an important regulator. In epithelial cells, Lulu2 is localized along apical cell-cell boundaries, and Lulu2 depletion by ribonucleic acid interference results in disorganization of the circumferential actomyosin belt. In its regulation of the belt, Lulu2 interacts with and activates p114RhoGEF, a Rho-specific guanine nucleotide exchanging factor (GEF), at apical cell-cell junctions. This interaction is negatively regulated via phosphorylation events in the FERM-adjacent domain of Lulu2 catalyzed by atypical protein kinase C. We further found that Patj, an apical cell polarity regulator, recruits p114RhoGEF to apical cell-cell boundaries via PDZ (PSD-95/Dlg/ZO-1) domain-mediated interaction. These findings therefore reveal a novel molecular system regulating the circumferential actomyosin belt in epithelial cells.
肌球蛋白 II 驱动的机械力控制上皮细胞的形状和形态发生。特别是位于顶端细胞-细胞连接处的圆周肌动球蛋白带，调节许多细胞过程。尽管它很重要，但调节带的分子机制还不完全清楚。在本文中，我们将果蝇 Yurt 同源的 FERM（4.1 蛋白，ezrin，radixin，moesin）结构域包含的分子 Lulu2 鉴定为一个重要的调节剂。在上皮细胞中，Lulu2 定位于顶端细胞-细胞边界，并且通过 RNA 干扰使 Lulu2 耗竭会导致圆周肌动球蛋白带的紊乱。在对带的调节中，Lulu2 在顶端细胞-细胞连接处与和激活 p114RhoGEF（Rho 特异性鸟嘌呤核苷酸交换因子 (GEF)）相互作用。这种相互作用通过 Lulu2 的 FERM 相邻结构域中的磷酸化事件负调节，该磷酸化事件由非典型蛋白激酶 C 催化。我们进一步发现，顶端细胞极性调节剂 Patj 通过 PDZ（PSD-95/Dlg/ZO-1）结构域介导的相互作用将 p114RhoGEF 招募到顶端细胞-细胞边界。因此，这些发现揭示了一个新的分子系统，调节上皮细胞中的圆周肌动球蛋白带。
