Sakamoto H, Broekelmann T, Cheresh D A, Ramirez F, Rosenbloom J, Mecham R P
Department of Cell Biology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Biol Chem. 1996 Mar 1;271(9):4916-22.
The fibrillins are large glycoprotein components of 10-nm microfibrils found in the extracellular matrix of most tissues. Microfibrils play a role in elastic fiber assembly and serve to link cells to elastic fibers in the extracellular matrix. To determine whether fibrillin-1 specifically interacts with receptors on cells from fibrillin-rich tissues, we evaluated whether two cell types that produce different types of fibrillin can adhere to purified fibrillin-1 in cell adhesion assays. Our results indicate that both cell types attach and spread on fibrillin-1 and that the RGD sequence in the fourth 8-cysteine motif mediates this interaction. Fibroblast attachment to fibrillin-1 was sensitive to inhibition by antibodies to the alphavbeta3 receptor and by peptides encoding the RGD sequence in fibrillin-1 and the second RGD sequence in fibrillin-2. In contrast, adhesion of auricular chondroblasts to fibrillin-1 was only partially inhibited by these reagents, suggesting that some cell types recognize a second, non-RGD binding site within the fibrillin molecule. These findings confirm and extend ultrastructural studies that suggest a direct interaction between microfibrils and the cell surface and provide a functional explanation for how this association occurs.
原纤蛋白是在大多数组织的细胞外基质中发现的10纳米微原纤维的大型糖蛋白成分。微原纤维在弹性纤维组装中发挥作用，并有助于将细胞与细胞外基质中的弹性纤维连接起来。为了确定原纤蛋白-1是否与富含原纤蛋白的组织中的细胞上的受体特异性相互作用，我们在细胞粘附试验中评估了两种产生不同类型原纤蛋白的细胞类型是否能粘附于纯化的原纤蛋白-1。我们的结果表明，两种细胞类型都能在原纤蛋白-1上附着并铺展，并且第四个8个半胱氨酸基序中的RGD序列介导了这种相互作用。成纤维细胞对原纤蛋白-1的附着对αvβ3受体抗体以及编码原纤蛋白-1中RGD序列和原纤蛋白-2中第二个RGD序列的肽的抑制敏感。相比之下，耳廓软骨细胞对原纤蛋白-1的粘附仅被这些试剂部分抑制，这表明某些细胞类型识别原纤蛋白分子内的第二个非RGD结合位点。这些发现证实并扩展了超微结构研究，这些研究表明微原纤维与细胞表面之间存在直接相互作用，并为这种关联的发生提供了功能解释。
