Vinexin family (SORBS) proteins play different roles in stiffness-sensing and contractile force generation
Vinexin family (SORBS) proteins play different roles in stiffness-sensing and contractile force generation
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DOI：
10.1242/jcs.200691
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发表时间：
2017-10-15
影响因子：
4
通讯作者：
Kioka, Noriyuki
中科院分区：
文献类型：
--
作者：
Ichikawa, Takafumi;Kita, Masahiro;Kioka, Noriyuki
Vinexin、c-Cbl相关蛋白（CAP）和Arg结合蛋白2（ArgBP 2）组成了一个被称为vinexin（SORBS）家族的衔接蛋白家族，该家族靶向粘着斑（FA）。虽然许多研究都集中在每一个SORBS蛋白，并部分阐明了他们参与mechanotransduction，他们的功能的比较分析还没有得到很好的解决。在这里，我们建立了小鼠胚胎成纤维细胞，单独表达SORBS蛋白，并在相同的细胞环境中分析其功能。vinexin-a和CAP都与黏着斑蛋白共定位于FA并促进富含黏着斑蛋白的FA的出现，而ArgBP 2与α-辅肌动蛋白共定位于FA的近端和肌动蛋白应力纤维（SF）上的点状结构，并诱导富含paxillin的FA。此外，vinexin-a和CAP都有助于细胞外基质硬度依赖性黏着斑蛋白行为，而ArgBP 2稳定SF上的α-辅肌动蛋白并增强细胞内收缩力。这些结果证明了SORBS蛋白在机械转导中的不同作用。
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-a and CAP co-localized with vinculin at FAs and promoted the appearance of vinculin-rich FAs, whereas ArgBP2 co-localized with a-actinin at the proximal end of FAs and punctate structures on actin stress fibers (SFs), and induced paxillin-rich FAs. Furthermore, both vinexin-a and CAP contributed to extracellular matrix stiffness-dependent vinculin behaviors, while ArgBP2 stabilized a-actinin on SFs and enhanced intracellular contractile forces. These results demonstrate the differential roles of SORBS proteins in mechanotransduction.