title: The junction-associated protein, zonula occludens-1, localizes to the nucleus before the maturation and during the remodeling of cell-cell contacts.
abstract: 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 distinct portions of the ZO-1 polypeptide reveal nuclear staining in subconfluent, 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 tissue sections of intestinal epithelial cells reveals nuclear labeling only along the outer tip of the villus. These results suggest that the 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 signal transduction.
authors.affiliation: Laboratory of Cell Signaling and Morphogenesis, UMR 144 Centre National de la Recherche Scientifique, Institut Curie, Paris, France.
authors.forename: C J
authors.initials: CJ
authors.lastname: Gottardi
authors.forename: M
authors.initials: M
authors.lastname: Arpin
authors.forename: A S
authors.initials: AS
authors.lastname: Fanning
authors.forename: D
authors.initials: D
authors.lastname: Louvard
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002451:Cell Compartmentation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004285:Dogs; D019084:Fluorescent Antibody Technique, Indirect; D051528:Guanylate Kinases; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins / Q000378:metabolism*; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D015398:Signal Transduction; D019108:Tight Junctions / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein
chemical_list: D008565:Membrane Proteins; D010750:Phosphoproteins; D062826:Zonula Occludens-1 Protein; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases