Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo, Kyoto 606-8502, Japan.
Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Sakyo, Kyoto 606-8507, Japan.
J Cell Sci. 2017 Oct 15;130(20):3517-3531. doi: 10.1242/jcs.200691. Epub 2017 Sep 1.
Vinexin, c-Cbl associated protein (CAP) and Arg-binding protein 2 (ArgBP2) constitute an adaptor protein family called the vinexin (SORBS) family that is targeted to focal adhesions (FAs). Although numerous studies have focused on each of the SORBS proteins and partially elucidated their involvement in mechanotransduction, a comparative analysis of their function has not been well addressed. Here, we established mouse embryonic fibroblasts that individually expressed SORBS proteins and analysed their functions in an identical cell context. Both vinexin-α and CAP co-localized with vinculin at FAs and promoted the appearance of vinculin-rich FAs, whereas ArgBP2 co-localized with α-actinin at the proximal end of FAs and punctate structures on actin stress fibers (SFs), and induced paxillin-rich FAs. Furthermore, both vinexin-α and CAP contributed to extracellular matrix stiffness-dependent vinculin behaviors, while ArgBP2 stabilized α-actinin on SFs and enhanced intracellular contractile forces. These results demonstrate the differential roles of SORBS proteins in mechanotransduction.
Vinexin、c-Cbl 相关蛋白 (CAP) 和 Arg 结合蛋白 2 (ArgBP2) 构成了一个称为 vinexin (SORBS) 家族的衔接蛋白家族，该家族定位于粘着斑 (FA)。虽然许多研究集中在 SORBS 蛋白的每一个上，并部分阐明了它们在机械转导中的参与，但它们的功能比较分析尚未得到很好的解决。在这里，我们建立了单独表达 SORBS 蛋白的小鼠胚胎成纤维细胞，并在相同的细胞环境中分析了它们的功能。Vinexin-α 和 CAP 均与粘着斑上的 vinculin 共定位，并促进 vinculin 丰富的粘着斑的出现，而 ArgBP2 与粘着斑近端的 α-辅肌动蛋白和肌动蛋白应力纤维 (SF) 上的点状结构共定位，并诱导富含桩蛋白的粘着斑。此外，Vinexin-α 和 CAP 均有助于细胞外基质刚度依赖性 vinculin 行为，而 ArgBP2 稳定 SF 上的 α-辅肌动蛋白并增强细胞内收缩力。这些结果表明 SORBS 蛋白在机械转导中具有不同的作用。
