Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Dev Cell. 2015 Oct 12;35(1):63-77. doi: 10.1016/j.devcel.2015.08.019. Epub 2015 Sep 24.
Adherens junctions (AJs) are membrane-anchored structures composed of E-cadherin and associated proteins, including catenins and actin. The unique plasticity of AJs mediates both the rigidity and flexibility of cell-cell contacts essential for embryonic morphogenesis and adult tissue remodeling. We identified the SUMO protease ULP-2 as a regulator of AJ assembly and show that dysregulated ULP-2 activity impairs epidermal morphogenesis in Caenorhabditis elegans embryos. The conserved cytoplasmic tail of HMR-1/E-cadherin is sumoylated and is a target of ULP-2 desumoylation activity. Coupled sumoylation and desumoylation of HMR-1 are required for its recruitment to the subapical membrane during AJ assembly and the formation of the linkages between AJs and the apical actin cytoskeleton. Sumoylation weakens HMR-1 binding to HMP-2/β-catenin. Our study provides a mechanistic link between the dynamic nature of the SUMO machinery and AJ plasticity and highlight sumoylation as a molecular switch that modulates the binding of E-cadherin to the actin cytoskeleton.
黏着连接（AJs）是由 E-钙黏蛋白和相关蛋白（包括连环蛋白和肌动蛋白）组成的膜锚定结构。AJs 的独特可塑性调节了细胞间连接的刚性和灵活性，这对于胚胎形态发生和成人组织重塑至关重要。我们鉴定出 SUMO 蛋白酶 ULP-2 是 AJ 组装的调节剂，并表明 ULP-2 活性失调会损害秀丽隐杆线虫胚胎的表皮形态发生。HMR-1/E-钙黏蛋白的保守细胞质尾巴被 SUMO 化，是 ULP-2 去 SUMO 化活性的靶标。在 AJ 组装过程中，HMR-1 的共 SUMO 化和去 SUMO 化对于其募集到亚顶膜以及 AJ 与顶端肌动蛋白细胞骨架之间的连接的形成是必需的。SUMO 化削弱了 HMR-1 与 HMP-2/β-连环蛋白的结合。我们的研究为 SUMO 机制的动态性质与 AJ 可塑性之间提供了一个机制联系，并强调了 SUMO 化作为调节 E-钙黏蛋白与肌动蛋白细胞骨架结合的分子开关的作用。
