BETA-1 INTEGRINS DO NOT HAVE A MAJOR ROLE IN KERATINOCYTE INTERCELLULAR-ADHESION

Integrins of the epidermis have been implicated both in intercellular adhesion and in cell-substratum adhesion. In the present study the rol e of alpha 2 beta 1 and alpha 3 beta 1 integrins has been evaluated fu rther using human keratinocyte culture. alpha 3 beta 1 but not alpha 2 beta 1 strongly colocalizes with talin in adhesion plaques, consisten t with a role for the former in adhesion to endogenous matrix. Upon el evation of the extracellular Ca2+ concentration from 30 mu M to 1.0 mM which is known to induce the organization of intercellular junctions, all three integrin subunits redistribute to concentrate along the cel l-cell borders, but alpha 3 redistributes more slowly. Blocking antibo dy to E-cadherin, which has previously been shown to delay the establi shment of cell-cell adhesion upon Ca2+ elevation, delays the redistrib ution of alpha 2 beta 1 and alpha 3 beta 1 integrins. Elevation of the Ca2+ concentration also induces a rapid morphological change in the k eratinocytes and organization of the culture into colonies with tight cell-cell connections. Blocking antibodies to beta 1 or to alpha 3, bu t not to alpha 2, delays this morphological change and the organizatio n into colonies; however, the effect is much more pronounced in subcon fluent cultures. These data are consistent with the hypothesis that an ti-beta 1 or anti-alpha 3 antibodies affect cell-cell interactions pri marily through their previously described inhibition of motility. Stra tification of the culture, which follows the formation of intercellula r interactions, is normal in the presence of blocking antibody to beta 1 integrin. In summary, these data suggest that integrins do not play a major role in intercellular keratinocyte adhesion, but may appear t o do so under certain conditions because of their involvement in motil ity. (C) 1995 Academic Press, Inc.