Lack of intrinsic polarity in the ligand-binding ability of keratinocyte beta1 integrins.
Within the basal layer of the epidermis the beta1 integrins have a pericellular distribution. Two monoclonal antibodies, 15/7 and 12G10, that detect a conformation of the beta1 integrin subunit that is induced following cation or ligand occupancy selectively recognized beta1 integrins at the basement membrane zone in vivo and in focal adhesions of cultured keratinocytes; they did not recognize integrins on the apical and upper lateral membranes of basal keratinocytes nor integrins on the suprabasal keratinocytes of hyperproliferative epidermis. Inhibition of intercellular adhesion did not induce the 15/7 epitope on the lateral and apical membrane domains. The surface distribution of the epitopes was consistent with the antibodies acting as reporters of ligand-binding; in addition, the 15/7 epitope was exposed on unglycosylated, immature beta1 integrins. Although the apical membrane of basal keratinocytes is not normally in contact with extracellular matrix proteins, we found that it was capable of binding fibronectin-coated beads and that the 15/7 epitope was exposed on plasma membrane in contact with the beads. When a chimeric molecule consisting of the extracellular domain of CD8 and the cytoplasmic domain of the beta1 integrin subunit, used to mimic a constitutively active beta1 heterodimer, was introduced into keratinocytes it localized to the basal, lateral and apical membrane domains. We conclude that although the conformation of the keratinocyte beta1 integrins differs between the basal and the lateral/apical membrane domains there is no intrinsic polarity in the ligand binding potential of the receptors.
Bishop
L A
LA
Keratinocyte Laboratory, Imperial Cancer Research Fund, London, UK.
Kee
W J
WJ
Zhu
A J
AJ
Watt
F M
FM
D001665:Binding Sites; D002448:Cell Adhesion; D016764:Cell Polarity; D002478:Cells, Cultured; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008024:Ligands; D011487:Protein Conformation
D019012:Integrin beta1; D008024:Ligands