The intracellular portion of an integrin dimer binds to a complex of several different proteins, which together form a linkage to the cytoskeleton. For all but one of the 24 varieties of human integrins, this intracellular linkage is to actin filaments. These linkages depend on proteins that assemble at the short cytoplasmic tails of the integrin subunits (see Figure 19–55). A large adaptor protein called talin is a component of the linkage in many cases, but numerous additional proteins are also involved. Like the actin-linked cell–cell junctions formed by cadherins, the actin-linked cell–matrix junctions formed by integrins may be small, inconspicuous, and transient, or large, prominent, and durable. Examples of the latter are the focal adhesions that form when fibroblasts have sufficient time to establish strong attachments to the rigid surface of a culture dish, and the myotendinous junctions that attach muscle cells to their tendons.
Figure 19–55 The subunit structure of an active integrin molecule, linking extracellular matrix to the actin cytoskeleton. the N-terminal heads of the integrin chains attach directly to an extracellular protein such as fibronectin;  the C-terminal intracellular tail of the integrin β subunit binds to adaptor proteins that interact with filamentous  actin. the best-understood adaptor is  a giant protein called talin, which contains a string of multiple domains for binding actin and other proteins, such as vinculin, that help reinforce and regulate the linkage to actin filaments. One end of talin binds to a specific site on the integrin β subunit cytoplasmic tail; other regulatory proteins, such as kindlin, bind at another site on the tail.
In epithelia, the most prominent cell–matrix attachment sites are the hemidesmosomes, where a specific type of integrin anchors the cells to laminin in the basal lamina. Here, uniquely, the intracellular attachment is to keratin intermediate filaments, via the intracellular adaptor proteins plectin and BP230 (Figure 19–56).
Integrin Defects are responsible for Many Genetic Diseases
Although there is some overlap in the activities of the different integrins—at least five bind laminin, for example—it is the diversity of integrin functions that is more remarkable. Table 19–3 lists some varieties of integrins and the problems that result when individual integrin αor β chains are defective.
The β1 subunit forms dimers with at least 12 distinct α subunits and is found on almost all vertebrate cells: α5β1 is a fibronectin receptor and α6β1 is a laminin
Figure 19–56 Hemidesmosomes.
(a) hemidesmosomes spot-weld epithelial cells to the basal lamina, linking laminin outside the cell to keratin filaments inside it. (B) Molecular components of a hemidesmosome. a specialized integrin (α6β4 integrin) spans the membrane, attaching to keratin filaments intracellularly via adaptor proteins called plectin and Bp230, and to laminin extracellularly. the adhesive complex also contains, in parallel with the integrin, an unusual collagen family member known as collagen type XVII; this has a membrane-spanning domain attached to its extracellular collagenous portion. Defects in any of these components can give rise to a blistering disease of the skin. One such disease, called bullous pemphigoid, is an autoimmune disease in which the immune system develops antibodies against collagen XVII or Bp230.
receptor on many types of cells. Mutant mice that cannot make any β1 integrins die early in embryonic development. Mice that are only unable to make the α7 subunit (the partner for β1 in muscle) survive but develop muscular dystrophy (as do mice that cannot make the laminin ligand for the α7β1 integrin).