Focal adhesions form a structural link between the actin cytoskeleton and extracellular matrix proteins. They are responsible for attaching long bundles of actin filaments (stress fibers) into the basal lamina (Fig. 5.35a). Focal adhesions play a prominent role during dynamic changes that occur in epithelial cells (e.g., migration of epithelial cells in wound repair). Coordinated remodeling of the actin cytoskeleton and the controlled formation and dismantling of focal adhesions provide the molecular bases for cell migration. Focal adhesions are also found in other nonepithelial cells such as fibroblasts and smooth muscle cells.
In general, focal adhesions consist of a cytoplasmic face to which actin flaments are bound, a transmembrane connecting region, and an extracellular face that binds to the proteins of the extracellular matrix. The main family of transmembrane proteins involved in focal adhesions are integrins, which are concentrated in clusters within the areas where the junctions can be detected. On the cytoplasmic face, integrins interact with actin-binding proteins (-actinin, vinculin, talin, paxillin) as well as many regulatory proteins such as focal adhesion kinase or tyrosine kinase (Fig. 5.35b). On the extracellular side, integrins bind to extracellular matrix glycoproteins, usually laminin and fibronectin.
FIGURE 5.35 • Molecular structure of focal adhesions. a. Diagram showing the molecular organization of focal adhesions. On the cytoplasmic side, note the arrangement of different actin-binding proteins. These proteins interact with integrins, the transmembrane proteins, the extracellular domains of which bind to proteins of the extracellular matrix (e.g., fibronectin). b. This image was obtained from the fluorescence microscope and shows cells cultured on the fibronectin-coated surface stained with fluoresceinlabeled phalloidin to visualize actin filaments (stress fibers) in green. Next, using indirect immunofluorescence techniques, focal adhesions were labeled with primary monoclonal antibody against phosphotyrosines and visualized with secondary rhodamine-labeled antibody (red). The phosphotyrosine is a product of the tyrosine kinase reaction in which tyrosine molecules of the associated proteins are phosphorylated by this enzyme. Tyrosine kinase is closely associated with focal adhesion molecules, so the area where focal adhesions are formed is labeled red. Note the relationship of focal adhesions and actin filaments at the periphery of the cell. 3,000. (Courtesy of Dr. Keith Burridge.)
Focal adhesions play an important role in sensing and transmitting signals from the extracellular environment into the interior of the cell.
Focal adhesions are also important sites of signal detection and transduction. They are able to detect contractile forces or mechanical changes in the extracellular matrix and convert them into biochemical signals. This phenomenon, known as mechanosensitivity, allows cells to alter their adhesion-mediated functions in response to external mechanical stimuli. Integrins transmit these signals to the interior of the cell, where they affect cell migration, differentiation, and growth. Recent studies indicate that focal adhesion proteins also serve as a common point of entry for signals resulting from stimulation of various classes of growth factor receptors.
Hemidesmosomes occur in epithelia that require strong, stable adhesion to the connective tissue.