D'Arrigo C, Burl S, Withers A P, Dobson H, Black C, Boxer M
Department of Neuropathology, Institute of Neurology, London, UK.
Connect Tissue Res. 1998;37(1-2):29-51. doi: 10.3109/03008209809028898.
Human fibrillin, a major component of the extracellular matrix, exists as two highly homologous forms (fibrillin-1 and -2). Several modules of fibrillin are homologous to TGF-beta1 binding protein. Two of these modules, D25 (the 25th module of fibrillin-1 and -2 D segment) and D12 (the 12th module of fibrillin-2 D segment) contain the cell adhesion motif arginyl-glycyl-aspartyl (RGD). The ability of RGD to mediate adhesion to D25-1 and D12-2 was investigated using bacterially expressed fusion proteins. Human skin fibroblasts and murine L-cells were used in microassays of cell attachment and cell spreading on fibrillin fusion-protein substrata. Dose-dependent experiments and competitive inhibition by soluble RGD-containing peptides demonstrated that D25-1 and D12-2 mediate RGD-dependent cell adhesion. These results provide evidence for a cell adhesion function of fibrillin-2. Inhibition with anti-integrin antibodies showed that alpha(v) and beta3 integrins mediate adhesion to D25-1, while alpha3, alpha(v) and beta1 are involved in adhesion to D12-2. Binding of different receptors may elicit distinct cell signalling supporting the hypothesis that fibrillin-1 and fibrillin-2 have distinct roles.
人原纤维蛋白是细胞外基质的主要成分，以两种高度同源的形式（原纤维蛋白-1和-2）存在。原纤维蛋白的几个模块与转化生长因子-β1结合蛋白同源。其中两个模块，D25（原纤维蛋白-1和-2 D段的第25个模块）和D12（原纤维蛋白-2 D段的第12个模块）含有细胞黏附基序精氨酰-甘氨酰-天冬氨酰（RGD）。使用细菌表达的融合蛋白研究了RGD介导与D25-1和D12-2黏附的能力。在原纤维蛋白融合蛋白基质上进行细胞附着和细胞铺展的微量测定中使用了人皮肤成纤维细胞和小鼠L细胞。剂量依赖性实验和含可溶性RGD肽的竞争性抑制表明，D25-1和D12-2介导RGD依赖性细胞黏附。这些结果为原纤维蛋白-2的细胞黏附功能提供了证据。用抗整合素抗体抑制表明，α(v)和β3整合素介导与D25-1的黏附，而α3、α(v)和β1参与与D12-2的黏附。不同受体的结合可能引发不同的细胞信号传导，支持原纤维蛋白-1和原纤维蛋白-2具有不同作用的假说。
