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

Craig T Lefort,Katherine Wojciechowski,Denise C Hocking

doi:10.1074/jbc.m110.115733

Craig T Lefort, Katherine Wojciechowski + Show 1 more

Open Access

https://doi.org/10.1074/jbc.m110.115733

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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 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 myofibroblasts, we identified a novel quaternary complex composed of N-cadherin, β-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 α5β1 integrins into nascent cell-cell adhesions. Initiation of fibronectin matrix assembly disrupted the association of tensin and actin with N-cadherin, released α5β1 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 α5β1 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 α5β1 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.

Highlights

Mediated cell-extracellular matrix (ECM) adhesion and cadherin-mediated cell-cell adhesion is required during tissue morphogenesis to facilitate the formation of functional, multicellular structures [1, 2]
To determine the effect of fibronectin on the organizational pattern of N-cadherin-dependent adherens junction (AJ), N-cadherin and ␤-catenin were immunolocalized in confluent FN-null cell monolayers treated with either fibronectin or the vehicle control, PBS
Both ␣5␤1 integrins, the major integrin receptor for fibronectin in fibroblasts [44], and tensin co-localized with N-cadherin in cell-cell contacts in the absence but not the presence of fibronectin

Summary

Introduction

Mediated cell-ECM adhesion and cadherin-mediated cell-cell adhesion is required during tissue morphogenesis to facilitate the formation of functional, multicellular structures [1, 2]. Our data indicate that fibronectin matrix polymerization transiently disrupts the interaction of N-cadherin-containing AJs with the actin cytoskeleton, stimulates the reorganization of cell-cell contacts, and decreases N-cadherin-mediated adhesion. We describe ␣5␤1 integrins and the actin-binding protein tensin as novel components of N-cadherin-based complexes formed in the absence of a fibronectin matrix and as possible targets for regulation of cell-cell adhesion by ECM fibronectin.

Results

Conclusion