N-cadherin Cell-Cell Adhesion Complexes Are Regulated by Fibronectin Matrix Assembly

Abstract

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 cellextracellular 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 myofibroblasts, we identified a novel quaternary complex composed of N-cadherin, ␤-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 ␣5␤1 integrins into nascent cell-cell adhesions. Initiation of fibronectin matrix assembly disrupted the association of tensin and actin with N-cadherin, released ␣5␤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 ␣5␤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 ␣5␤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.Tissue development, remodeling, and homeostasis are governed by adhesion of cells to extracellular matrix (ECM) 3 and to neighboring cells (1). Tight coordination between integrinmediated cell-ECM adhesion and cadherin-mediated cell-cell adhesion is required during tissue morphogenesis to facilitate the formation of functional, multicellular structures (1, 2). Cell adhesion to ECM proteins has been shown to affect the expression, localization, composition, and function of cell-cell adhesions (2). However, neither the intracellular nor extracellular mechanisms that serve to coordinate the activities of these two adhesion systems are well understood. The adhesive functions of both integrins and cadherins require interactions with the actin cytoskeleton (3, 4). Further, the intracellular protein complexes that link integrins and cadherins to the actin cytoskeleton share several molecular components, including ␣-actinin and vinculin (3). As such, the exchange or sequestration of molecular constituents that are common to both adhesion systems provides an attractive mechanism by which cell-ECM adhesion can influence cell-cell adhesion and vice versa.Cadherins are a family of transmembrane receptors that mediate calcium-dependent cell-cell adhesion by homophilic association of their ectodomains (3). The cadher...

Cross-Scale Integrin Regulation Organizes ECM and Tissue Topology

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Fibronectin matrix assembly is essential for cell condensation during chondrogenesis

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Rare autosomal copy number variations in early-onset familial Alzheimer’s disease

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