title: Nuclear Zonula occludens-2 alters gene expression and junctional stability in epithelial and endothelial cells.
abstract: Zonula occludens proteins (ZOPs) are essential scaffold proteins involved in the organization of epithelial and endothelial intercellular junctions. Based on their molecular domain architecture, they are members of the large family of membrane-associated guanylate kinase-like (MAGUK) proteins. As all other MAGUKs, ZOPs contain a core of several PDZ, an src homology-3, and a guanylate kinase-like domain, indicating that these proteins may serve both structural and signaling functions. In addition, ZOPs exhibit some unique motifs not shared by other MAGUKs, i.e., several nuclear localization (NLS) and nuclear export signals (NES), allowing these proteins to shuttle between the cytoplasm and the nucleus. However, the stimuli leading to the nuclear accumulation of ZOPs and the resulting physiological consequences remain poorly defined. We have previously reported the direct binding of nuclear ZO-2 to scaffold attachment factor B, a heterogeneous nuclear ribonucleoprotein involved in chromatin organization and the transcriptional control of eukaryotic genes. We now report that the nuclear accumulation of ZO-2 leads to an increase in the expression of the M2 type of pyruvate kinase (M2-PK) in epithelial and endothelial cells. Further, the proliferative activity was increased, while the intercellular junctional stability of Madin-Darby canine kidney cells was reduced. Our data provide evidence to suggest that ZO-2 exerts a junction-unrelated function that further supports the notion of a general "dual" role of junctional MAGUKs, being an indispensable structural component at cell-cell junctions and a nuclear factor influencing gene expression and cell behavior.
authors.affiliation: Developmental Biology Group, Department of Organismic Biology, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Traweger
authors.forename: Christine
authors.initials: C
authors.lastname: Lehner
authors.forename: Attila
authors.initials: A
authors.lastname: Farkas
authors.forename: István Adorján
authors.initials: IA
authors.lastname: Krizbai
authors.forename: Herbert
authors.initials: H
authors.lastname: Tempfer
authors.forename: Eva
authors.initials: E
authors.lastname: Klement
authors.forename: Brigitte
authors.initials: B
authors.lastname: Guenther
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Bauer
authors.forename: Hannelore
authors.initials: H
authors.lastname: Bauer
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D004285:Dogs; D042783:Endothelial Cells / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D007365:Intercellular Junctions / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000096:biosynthesis; D014162:Transfection; D062827:Zonula Occludens-2 Protein
chemical_list: D008565:Membrane Proteins; D009687:Nuclear Proteins; D062827:Zonula Occludens-2 Protein; D011770:Pyruvate Kinase