αV-integrins are required for mechanotransduction in MDCK epithelial cells

• Published in: PloS one 2013-08, Vol.8 (8), p.e71485-e71485
• Main Authors: Teräväinen, Terhi P, Myllymäki, Satu M, Friedrichs, Jens, Strohmeyer, Nico, Moyano, Jose V, Wu, Chuanyue, Matlin, Karl S, Muller, Daniel J, Manninen, Aki
• Format: Article
• Language: English
• Subjects: Actin; Adhesion; Analysis; Animals; Biochemistry; Biology; Cell adhesion & migration; Cell Adhesion - drug effects; Cell cycle; Cell migration; Cell Movement - drug effects; Cell spreading; Collagen; Collagen (type I); Collagen Type I - pharmacology; Cytoskeleton; Dismantling; Dogs; Enzyme Activation - drug effects; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Extracellular matrix; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Focal adhesion kinase; Focal Adhesion Protein-Tyrosine Kinases - metabolism; Focal Adhesions - drug effects; Focal Adhesions - metabolism; Gene Knockdown Techniques; ILK protein; Integrin alphaV - metabolism; Integrin beta1 - metabolism; Integrins; Laminin - metabolism; Ligands; Madin Darby Canine Kidney Cells; Mechanical properties; Mechanotransduction; Mechanotransduction, Cellular - drug effects; Mice; Molecular biology; Muscle proteins; Oligopeptides - metabolism; Pathogenesis; Physiology; Protein Binding - drug effects; Substrates; Talin; Tissues; Vinculin
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0071485

The properties of epithelial cells within tissues are regulated by their immediate microenvironment, which consists of neighboring cells and the extracellular matrix (ECM). Integrin heterodimers orchestrate dynamic assembly and disassembly of cell-ECM connections and thereby convey biochemical and mechanical information from the ECM into cells. However, the specific contributions and functional hierarchy between different integrin heterodimers in the regulation of focal adhesion dynamics in epithelial cells are incompletely understood. Here, we have studied the functions of RGD-binding αV-integrins in a Madin Darby Canine Kidney (MDCK) cell model and found that αV-integrins regulate the maturation of focal adhesions (FAs) and cell spreading. αV-integrin-deficient MDCK cells bound collagen I (Col I) substrate via α2β1-integrins but failed to efficiently recruit FA components such as talin, focal adhesion kinase (FAK), vinculin and integrin-linked kinase (ILK). The apparent inability to mature α2β1-integrin-mediated FAs and link them to cellular actin cytoskeleton led to disrupted mechanotransduction in αV-integrin deficient cells seeded onto Col I substrate.