Ruisu Katrin, Meier Riho, Kask Keiu, Tõnissoo Tambet, Velling Teet, Pooga Margus
Department of Developmental Biology, Institute of Molecular and Cell Biology, University of Tartu, 23 Riia St., Tartu 51010, Estonia.
Department of Developmental Biology, Institute of Molecular and Cell Biology, University of Tartu, 23 Riia St., Tartu 51010, Estonia; Competence Centre on Health Technologies, Tiigi 61b, 50410 Tartu, Estonia.
Exp Cell Res. 2017 Aug 15;357(2):181-191. doi: 10.1016/j.yexcr.2017.05.012. Epub 2017 May 16.
RIC8A functions as a chaperone and guanine nucleotide exchange factor for a subset of G protein α subunits. Multiple G protein subunits mediate various signalling events that regulate cell adhesion and migration and the involvement of RIC8A in some of these processes has been demonstrated. We have previously shown that the deficiency of RIC8A causes a failure in mouse gastrulation and neurogenesis - major events in embryogenesis that rely on proper association of cells with the extracellular matrix (ECM) and involve active cell migration. To elaborate on these findings, we used Ric8a mouse embryonic stem cells and Ric8a-deficient mouse embryonic fibroblasts, and found that RIC8A plays an important role in the organisation and remodelling of actin cytoskeleton and cell-ECM association. Ric8a-deficient cells were able to attach to different ECM components, but were unable to spread correctly, and did not form stress fibres or focal adhesion complexes. We also found that the presence of RIC8A is necessary for the activation of β1 integrins and integrin-mediated cell migration.
RIC8A作为伴侣蛋白和鸟嘌呤核苷酸交换因子，作用于G蛋白α亚基的一个子集。多个G蛋白亚基介导各种信号事件，这些事件调节细胞黏附和迁移，并且已证明RIC8A参与其中一些过程。我们之前已经表明，RIC8A的缺失会导致小鼠原肠胚形成和神经发生失败，这是胚胎发育中的主要事件，依赖于细胞与细胞外基质（ECM）的正确结合，并涉及活跃的细胞迁移。为了详细阐述这些发现，我们使用了Ric8a小鼠胚胎干细胞和Ric8a缺陷型小鼠胚胎成纤维细胞，发现RIC8A在肌动蛋白细胞骨架的组织和重塑以及细胞与ECM的结合中起重要作用。Ric8a缺陷型细胞能够附着于不同的ECM成分，但无法正确铺展，也不形成应力纤维或粘着斑复合体。我们还发现，RIC8A的存在对于β1整合素的激活和整合素介导的细胞迁移是必要的。
