Cell Adhesion And Signaling Transduction

Extracellular matrix (ECM) is a generic term encompassing mixtures of polysaccharides and proteins, including collagens, fibronectins, laminins, and proteoglycans, all secreted by the cell.

Extracellular matrix (ECM) provides a route for cell migrations, and molecules in the matrix activate classic signal-transduction pathways that induce cell growth, proliferation, and gene expression. These many effects of the matrix involve membrane-bound CAMs that bind directly to components of the ECM and the cytoskeleton.

Cells attach to the underlying extracellular matrix through two types of integrin-dependent junctions: focal adhesions, which attach the actin cytoskeleton to fibers of fibronectin, and hemidesmosomes, which connect intermediate filaments to basal laminae.

Focal Adhesions

Activation of fibroblasts in the Rho signaling pathway causes the formation of abundant actin-rich stress fibers, which help maintain the cells' shapes and adhere them to the substratum. Actin filaments of the stress fibers are attached to the β subunit of integrins through adapter proteins; these peripheral membrane proteins, including vinculin, are generally located in the region of the cytosol just inside the plasma membrane.

Integrins cluster to assemble a focal adhesion. This process is mediated by tension exerted on actin filaments by myosin II. More than 20 proteins — actin-binding proteins, kinases, and membrane-binding proteins — are also localized in focal adhesions. They function to activate adhesion-dependent signals for cell growth and cell motility.

The role of integrin in mediating interactions with the cytoskeleton was first suggested by fluorescence microscopy of cultured fibroblasts showing the colocalization of stress fibers and α5β1 integrin. In some sections, exterior fibronectin fiber bundles appear continuous with bundles of actin fibers within the cell. Thus integrin α5β1, localized to focal adhesions, anchors the two types of fibers to the opposite sides of the plasma membrane.

Hemidesmosomes

The second type of cell-matrix adhesion junction, the hemidesmosome, is found mainly on the basal surface of epithelial cells. These junctions firmly anchor epithelial cells to the underlying basal lamina. The cytosolic side of a hemidesmosome consists of a plaque composed of adapter proteins, which are attached to the ends of keratin filaments.

Integrin α6β4 is localized to hemidesmosomes and is thought to bind to an adapter protein, plectin, within the plaques and to the extracellular-matrix protein laminin. By interconnecting the intermediate filaments of the cytoskeleton with the fibers of the basal lamina, these cell-matrix junctions increase the overall rigidity of epithelial tissues.