Cytoplasmic and transmembrane domains of integrin β1 and β3 subunits are functionally interchangeable

Abstract

Integrin βsubunits combine with specific sets of α subunits to form functional adhesion receptors. The structure and binding properties of integrins suggest the presence of domains controlling at least three major functions: subunit association, ligand binding, and cytoskeletal interactions. To more carefully define structure/function relationships, a cDNA construct consisting of the extracellular domain of the avian β1 subunit and the cytoplasmic and transmembrane domains of the human β3 subunit was prepared and expressed in murine 3T3 cells. The resulting chimetric β1/3 subunit formed heterodimers with α subunits from the β1 subfamily, could not interact with αIIb, from the β3 subfamily, was targeted to focal contacts, and formed functional complexes within the focal contacts. A second cDNA construct was prepared that coded for an avian β1 subunit without a transmembrane or cytoplasmic domain. This subunit was not found in association with an accompanying α subunit, nor was it found expressed on the cell surface. Instead, it accumulated in vesicles within the cytoplasm and was eventually shed from the cell. The results from studies of the behavior of these two cDNA constructs demonstrate that the transmembrane and cytoplasmic domains play no role in a subunit selection, that the cytoplasmic domain of β3 is capable of functioning in the context of α subunits with which it is not normally paired, and that both integrin subunits must be membrane associated for normal assembly and transport to cell surface adhesive structures.