title: Cytoplasmic and transmembrane domains of integrin beta 1 and beta 3 subunits are functionally interchangeable.
abstract: Integrin beta subunits combine with specific sets of alpha 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 beta 1 subunit and the cytoplasmic and transmembrane domains of the human beta 3 subunit was prepared and expressed in murine 3T3 cells. The resulting chimeric beta 1/3 subunit formed heterodimers with alpha subunits from the beta 1 subfamily, could not interact with alpha IIb from the beta 3 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 beta 1 subunit without a transmembrane or cytoplasmic domain. This subunit was not found in association with an accompanying alpha 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 alpha subunit selection, that the cytoplasmic domain of beta 3 is capable of functioning in the context of alpha 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.
authors.affiliation: Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
authors.forename: J
authors.initials: J
authors.lastname: Solowska
authors.forename: J M
authors.initials: JM
authors.lastname: Edelman
authors.forename: S M
authors.initials: SM
authors.lastname: Albelda
authors.forename: C A
authors.initials: CA
authors.lastname: Buck
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D003593:Cytoplasm / Q000648:ultrastructure; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004252:DNA Mutational Analysis; D005455:Fluorescent Antibody Technique; D006801:Humans; D007158:Immunologic Techniques; D016023:Integrins / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure; D046911:Macromolecular Substances; D015394:Molecular Structure; D011993:Recombinant Fusion Proteins; D013329:Structure-Activity Relationship; D014162:Transfection; D016596:Vinculin
chemical_list: D003598:Cytoskeletal Proteins; D016023:Integrins; D046911:Macromolecular Substances; D011993:Recombinant Fusion Proteins; D016596:Vinculin