THE JUNCTION-ASSOCIATED PROTEIN, ZONULA OCCLUDENS-1, LOCALIZES TO THENUCLEUS BEFORE THE MATURATION AND DURING THE REMODELING OF CELL-CELL CONTACTS

The junction-associated protein zonula occludens-1 (ZO-1) is a member of a family of membrane-associated guanylate kinase homologues thought to be important in signal transduction at sites of cell-cell contact, We present evidence that under certain conditions of cell growth, ZO- 1 can be detected in the nucleus, Two different antibodies against dis tinct portions of the ZO-1 polypeptide reveal nuclear staining in subc onfluent, but not confluent, cell cultures, An exogenously expressed, epitope-tagged ZO-1 can also be detected in the nuclei of transfected cells, Nuclear accumulation can be stimulated at sites of wounding in cultured epithelial cells, and immunoperoxidase detection of ZO-1 in t issue sections of intestinal epithelial cells reveals nuclear labeling only along the outer tip of the villus, These results suggest that th e nuclear localization of ZO-1 is inversely related to the extent and/ or maturity of cell contact, Since cell-cell contacts are specialized sites for signaling pathways implicated in growth and differentiation, we suggest that the nuclear accumulation of ZO-1 may be relevant for its suggested role in membrane-associated guanylate kinase homologue s ignal transduction.