N-cadherin Cell-Cell Adhesion Complexes Are Regulated by Fibronectin Matrix Assembly
N-cadherin Cell-Cell Adhesion Complexes Are Regulated by Fibronectin Matrix Assembly
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DOI：
10.1074/jbc.m110.115733
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发表时间：
2011-01-28
影响因子：
4.8
通讯作者：
Hocking, Denise C.
中科院分区：
文献类型：
--
作者：
Lefort, Craig T.;Wojciechowski, Katherine;Hocking, Denise C.
纤维连接蛋白是细胞外基质的主要成分。可溶性纤维连接蛋白分子通过细胞依赖的过程以不溶的纤维链的形式组装到细胞外基质中。反过来，细胞与细胞外基质形式的纤维连接蛋白的相互作用刺激了对组织修复至关重要的细胞功能。在胚胎发育和组织重塑过程中，细胞-细胞和细胞-细胞外基质黏附复合体之间的串扰对于将细胞组织成复杂的、功能组织是必不可少的。在这里，我们证明纤维连接蛋白基质组装影响基于N-钙粘附素的黏附连接的组织、组成和功能。利用纤维连接蛋白缺失的小鼠胚胎肌成纤维细胞，我们鉴定了一种新的四元复合体，它由N-钙粘蛋白、β-连环素、张力蛋白和肌动蛋白组成，在没有纤维连接蛋白基质的情况下存在。在没有纤维连接蛋白的情况下，高亲和性N-钙粘连蛋白结扎将张力蛋白和α5β1整合素招募到新生细胞-细胞粘连中。纤维连接蛋白基质组装的启动破坏了张力蛋白和肌动蛋白与N-钙粘附素的结合，从细胞-细胞接触中释放出α5β1整合素和张力蛋白，刺激N-钙粘附素重组为薄的细胞突起，并减少了N-钙粘附素的粘附性。纤维连接蛋白基质组装已被证明可以将α5β1整合素和紧张素招募到纤维粘连中。综上所述，这些研究表明，张力蛋白是基于整合素和钙粘附素的粘连的共同细胞骨架纽带，在纤维连接蛋白基质组装过程中，α5β1整合素从细胞-细胞接触转移到纤维粘连是协调细胞-细胞和细胞-基质粘连的一种新机制。
Fibronectin is a principal component of the extracellular matrix. Soluble fibronectin molecules are assembled into the extracellular matrix as insoluble, fibrillar strands via a cell-dependent process. In turn, the interaction of cells with the extracellular matrix form of fibronectin stimulates cell functions critical for tissue repair. Cross-talk between cell-cell and cell-extracellular matrix adhesion complexes is essential for the organization of cells into complex, functional tissue during embryonic development and tissue remodeling. Here, we demonstrate that fibronectin matrix assembly affects the organization, composition, and function of N-cadherin-based adherens junctions. Using fibronectin-null mouse embryonic myofibro-blasts, we identified a novel quaternary complex composed of N-cadherin, beta-catenin, tensin, and actin that exists in the absence of a fibronectin matrix. In the absence of fibronectin, homophilic N-cadherin ligation recruited both tensin and alpha 5 beta 1 integrins into nascent cell-cell adhesions. Initiation of fibronectin matrix assembly disrupted the association of tensin and actin with N-cadherin, released alpha 5 beta 1 integrins and tensin from cell-cell contacts, stimulated N-cadherin reorganization into thin cellular protrusions, and decreased N-cadherin adhesion. Fibronectin matrix assembly has been shown to recruit alpha 5 beta 1 integrins and tensin into fibrillar adhesions. Taken together, these studies suggest that tensin serves as a common cytoskeletal link for integrin- and cadherin-based adhesions and that the translocation of alpha 5 beta 1 integrins from cell-cell contacts into fibrillar adhesions during fibronectin matrix assembly is a novel mechanism by which cell-cell and cell-matrix adhesions are coordinated.