CEACAM1 isoforms with different cytoplasmic domains show different localization, organization and adhesive properties in polarized epithelial cells

Abstract

CEACAM1 is a signaling cell adhesion molecule expressed in epithelia,vessel endothelia and leukocytes. It is expressed as two major isoforms with different cytoplasmic domains. CEACAM1 occurs both in cell-cell contact areas and on apical surfaces of polarized epithelial cells, but it is not known how the different isoforms are distributed in polarized cells or what the functions of CEACAM1 are in the apical surfaces. We investigated the localization and organization of the two CEACAM1 isoforms in transfected,polarized MDCK cells by confocal microscopy and differential surface labelling. CEACAM1-L was found on both the apical and the lateral surfaces,whereas CEACAM1-S appeared exclusively on the apical surfaces. Maintenance of the lateral localization of CEACAM1-L required homophilic binding between CEACAM1-L molecules on adjacent cells. Double-labelling with anti-CEACAM1 antibodies directed against different epitopes indicated that apical CEACAM1-L occurred either in a homophilic adhesive state or in a free non-adhesive state. CEACAM1-S appeared almost exclusively in the homophilic adhesive state. These findings suggest that CEACAM1 mediates adhesive bonds between adjacent microvilli on the apical surfaces.