Novel function for beta 1 integrins in keratinocyte cell-cell interactions.
We have examined the expression, localization, and function of beta 1 integrins on cultured human epidermal keratinocytes using polyclonal and monoclonal antibodies against the beta 1, alpha 2, alpha 3, and alpha 5 integrin subunits. The beta 1 polypeptide, common to all class 1 integrins, was localized primarily in areas of cell-cell contacts of cultured keratinocytes, as were alpha 2 and alpha 3 polypeptides, suggesting a possible role in cell-cell adhesion for these integrin polypeptides. In contrast, the fibronectin receptor alpha 5 subunit showed no such accumulations in regions of cell-cell contact but was more diffusely distributed in the keratinocyte plasma membrane, consistent with the absence of fibronectin at cell-cell contact sites. Colonies of cultured keratinocytes could be dissociated by treatment with monoclonal antibody specific to the beta 1 polypeptide. Such dissociation of cell-cell contacts also occurred under conditions where the monoclonal antibody had no effect on cell-substrate adhesion. Therefore, beta 1 integrin-dependent cell-cell adhesion can be inhibited without affecting other cell-adhesive interactions. Antibody treatment of keratinocytes maintained in either low (0.15 mM) or high (1.2 mM) CaCl2 also resulted in the loss of organization of intracellular F-actin filaments and beta 1 integrins, even when the anti-beta 1 monoclonal antibody had no dissociating effect on keratinocyte colonies at the higher calcium concentration. Our results indicate that beta 1 integrins play roles in the maintenance of cell-cell contacts between keratinocytes and in the organization of intracellular microfilaments. They suggest that in epithelial cells integrins can function in cell-cell interactions as well as in cell-substrate adhesion.
Membrane Biochemistry Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
H
H
Larjava
J
J
Peltonen
S K
SK
Akiyama
S S
SS
Yamada
H R
HR
Gralnick
J
J
Uitto
K M
KM
Yamada
D000199:Actins / Q000502:physiology; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion; D002478:Cells, Cultured; D005347:Fibroblasts / Q000502:physiology; D005353:Fibronectins / Q000502:physiology; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015603:Keratinocytes / Q000502:physiology*; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D019096:Vitronectin
D000199:Actins; D000911:Antibodies, Monoclonal; D005353:Fibronectins; D006023:Glycoproteins; D016023:Integrins; D046911:Macromolecular Substances; D019096:Vitronectin