Richard N. Tamura

A novel integrin (alpha E beta 4) from human epithelial cells suggests a fourth family of integrin adhesion receptors.

A new member of the integrin superfamily of adhesion receptors was isolated from human epithelial cells. Analogously to other integrins, this molecule is a heterodimer comprised of structurally unrelated subunits, both glycosylated. Unequivocal amino‐acid sequence homologies were observed between these subunits and integrin alpha and beta chain sequences, indicating that this epithelial heterodimer is a novel integrin. No obvious serologic cross‐reactivities were detected with other integrins. The beta chain of the epithelial integrin displayed a mol. wt significantly higher than other integrin beta chains, possibly due to a large sialic acid content. Integrin heterodimers are grouped into three families, based on which of three beta chains (beta 1, beta 2 and beta 3) they contain. Therefore, the epithelial integrin may represent the prototype of a fourth integrin family, because it contains a structurally distinct beta chain. The designation alpha E beta 4 is proposed for this novel human integrin.

Distinctive Functions of α6β4 and Other Integrins in Epithelial Cells

Publisher Summary This chapter discusses the aspects of structure and function of β4, β1, and αV integrins that are relevant to epithelial cells. Integrin α6β4 acts as a link between basement membrane and the intermediate filament cytoskeleton in epithelial cells. A proper identification of the α6β4 ligand will be an important step that may clarify many aspects of the molecular interactions between epithelial cells and basement membranes. Several laboratories concurrently produced evidence that α6β4 in epithelial cells is physically associated with structures termed hemidesmosomes. It has been speculated that α6β4 has a role in catalyzing the reorganization of hemidesmosomal components, perhaps after the recognition of a ligand in the basement membrane. Although α6β4 is diffusely distributed throughout the cytoplasm of migrating epithelial cells, as soon as migration halts, it becomes quickly polarized to the basal surface in areas of contact with the basement membrane. In addition, there is a consistent distribution of expression in carcinomas from a variety of sources. Interestingly, α6β4 appears to be expressed in carcinoma cells whether or not the normal tissue of origin is α6β4 positive.