Identification of specific human epithelial cell integrin receptors as VLA proteins.
Cell adhesion to extracellular matrix is mediated by a set of heterodimeric cell surface receptors called integrins. We have examined the expression of the very late antigens or alpha beta 1 group of integrins in human epithelial cells. The six known members of this group share a common beta 1 subunit but have distinct alpha subunits that confer selective affinity toward collagen, fibronectin, and laminin essentially. Using a panel of specific antibodies we showed that freshly harvested human epidermal basal cells express VLA-2 and VLA-3 receptors, a low amount of VLA-5, but fail to express VLA-4. The findings reveal that these receptors are characterized by the alpha subunits which associate with a beta subunit different in weight (Mr 110,000 reduced) from that normally seen (Mr 130,000). Moreover, immunoprecipitates of VLA-2 contained additional proteins of Mr 80,000 and Mr 40,000 and immunoprecipitates of VLA-3 contained an additional protein of Mr 90,000. Experiments carried out to investigate the functional roles of these receptors in mediating cell adhesion to extracellular matrix revealed that cell attachment to type IV collagen was completely inhibited by antibodies to VLA-2 alpha chain, that antibody to VLA-3 alpha chain significantly blocked attachment to fibronectin while antibodies to both VLA-2 and VLA-3 partially inhibited attachment to type I collagen. Cell attachment to types I and IV collagen and to fibronectin was not affected by antibodies to VLA-4 and VLA-6. These results show that multiple VLA receptors function in combination to mediate epidermal basal cell adhesion to extracellular matrix. This cooperation function of multiple VLA receptors and their differential expression could be considered to be one of the controlling points in the localization of epithelial basal cells in the epidermis.
Staquet
M J
MJ
CNRS URA 601, INSERM U 209, Hôpital Edouard-Herriot, Lyon, France.
Levarlet
B
B
Dezutter-Dambuyant
C
C
Schmitt
D
D
Thivolet
J
J
D000911:Antibodies, Monoclonal; D002448:Cell Adhesion; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D004817:Epidermis / Q000032:analysis* / Q000276:immunology / Q000502:physiology; D004848:Epithelium / Q000032:analysis / Q000276:immunology / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D046911:Macromolecular Substances; D008970:Molecular Weight; D016029:Receptors, Very Late Antigen / Q000032:analysis*
D000911:Antibodies, Monoclonal; D046911:Macromolecular Substances; D016029:Receptors, Very Late Antigen