Physical state of the extracellular matrix regulates the structure and molecular composition of cell-matrix adhesions
Physical state of the extracellular matrix regulates the structure and molecular composition of cell-matrix adhesions
复制标题
DOI：
10.1091/mbc.11.3.1047
复制
发表时间：
2000-03-01
影响因子：
3.3
通讯作者：
Geiger, B
中科院分区：
文献类型：
--
作者：
Katz, BZ;Zamir, E;Geiger, B
本研究证实细胞外基质的物理状态可以调节整合素介导的细胞骨架组装和酪氨酸磷酸化，从而产生两种不同类型的细胞-基质粘附。在原代成纤维细胞中，α (5) β(1)整合素主要与纤维连接蛋白原纤维结合，形成与局灶性接触结构不同的粘附，独立于肌动球蛋白介导的细胞收缩性。这些“纤维粘连”富含紧张素，但含有低水平的典型局灶接触成分paxillin、vinculin和酪氨酸磷酸化蛋白。然而，当纤维连接蛋白与底物共价连接时，α (5) β(1)整合素形成高度酪氨酸磷酸化的“经典”局灶接触，含有高水平的帕西林和维culin。这些实验表明，基质的物理状态，而不仅仅是其分子组成，是定义细胞骨架组织和粘附位点磷酸化的关键因素。我们提出，粘附位点的分子组织至少由两种机制控制：1)特异性整合素与其配体在跨膜复合物中与适当的细胞质锚定蛋白（例如，纤维连接蛋白- α （5) β(1)整合素-紧张素复合物）相结合；2）细胞外基质的物理性质（例如，刚性）调节粘附位点的局部张力，激活局部酪氨酸磷酸化，招募各种斑块分子到这些位点。这些机制在成纤维细胞中产生结构和功能上不同类型的基质粘附。
This study establishes that the physical state of the extracellular matrix can regulate integrin-mediated cytoskeletal assembly and tyrosine phosphorylation to generate two distinct types of cell-matrix adhesions. In primary fibroblasts, alpha(5)beta(1) integrin associates mainly with fibronectin fibrils and forms adhesions structurally distinct from focal contacts, independent of actomyosin-mediated cell contractility. These "fibrillar adhesions" are enriched in tensin, but contain low levels of the typical focal contact components paxillin, vinculin, and tyrosine-phosphorylated proteins. However, when the fibronectin is covalently linked to the substrate, alpha(5)beta(1) integrin forms highly tyrosine-phosphorylated, "classical" focal contacts containing high levels of paxillin and vinculin. These experiments indicate that the physical state of the matrix, not just its molecular composition, is a critical factor in defining cytoskeletal organization and phosphorylation at adhesion sites. We propose that molecular organization of adhesion sites is controlled by at least two mechanisms: 1) specific integrins associate with their ligands in transmembrane complexes with appropriate cytoplasmic anchor proteins (e.g., fibronectin-alpha(5)beta(1) integrin-tensin complexes), and 2) physical properties (e.g., rigidity) of the extracellular matrix regulate local tension at adhesion sites and activate local tyrosine phosphorylation, recruiting a variety of plaque molecules to these sites. These mechanisms generate structurally and functionally distinct types of matrix adhesions in fibroblasts.