title: Beyond cell-cell adhesion: Emerging roles of the tight junction scaffold ZO-2.
abstract: Zonula occludens proteins (ZO-1, ZO-2, ZO-3), which belong to the family of membrane-associated guanylate kinase (MAGUK) homologs, serve as molecular hubs for the assembly of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. These multi-PDZ proteins exert crucial functions in the structural organization of intercellular contacts and in transducing intracellular signals from the plasma membrane to the nucleus. The junctional MAGUK protein ZO-2 not only associates with the C-terminal PDZ-binding motif of various transmembrane junctional proteins but also transiently targets to the nucleus and interacts with a number of nuclear proteins, thereby modulating gene expression and cell proliferation. Recent evidence suggests that ZO-2 is also involved in stress response and cytoprotective mechanisms, which further highlights the multi-faceted nature of this PDZ domain-containing protein. This review focuses on ZO-2 acting as a molecular scaffold at the cytoplasmic aspect of tight junctions and within the nucleus and discusses additional aspects of its cellular activities. The multitude of proteins interacting with ZO-2 and the heterogeneity of proteins either influencing or being influenced by ZO-2 suggests an exceptional functional capacity of this protein far beyond merely serving as a structural component of cellular junctions.
authors.affiliation: Paracelsus Medical University; Spinal Cord Injury and Tissue Regeneration Center Salzburg; Institute of Tendon and Bone Regeneration; Salzburg, Austria ; Austrian Cluster for Tissue Regeneration; Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Traweger
authors.affiliation: University of Salzburg; Department of Organismic Biology; Salzburg, Austria.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Toepfer
authors.affiliation: Sanford-Burnham Medical Research Institute; La Jolla, CA USA.
authors.forename: Roland N
authors.initials: RN
authors.lastname: Wagner
authors.affiliation: University of Salzburg; Department of Organismic Biology; Salzburg, Austria.
authors.forename: Josef
authors.initials: J
authors.lastname: Zweimueller-Mayer
authors.affiliation: Paracelsus Medical University; Spinal Cord Injury and Tissue Regeneration Center Salzburg; Institute of Tendon and Bone Regeneration; Salzburg, Austria ; Austrian Cluster for Tissue Regeneration; Vienna, Austria.
authors.forename: Renate
authors.initials: R
authors.lastname: Gehwolf
authors.affiliation: Paracelsus Medical University; Spinal Cord Injury and Tissue Regeneration Center Salzburg; Institute of Tendon and Bone Regeneration; Salzburg, Austria ; Austrian Cluster for Tissue Regeneration; Vienna, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Lehner
authors.affiliation: Paracelsus Medical University; Spinal Cord Injury and Tissue Regeneration Center Salzburg; Institute of Tendon and Bone Regeneration; Salzburg, Austria ; Austrian Cluster for Tissue Regeneration; Vienna, Austria.
authors.forename: Herbert
authors.initials: H
authors.lastname: Tempfer
authors.affiliation: Institute of Biophysics; Biological Research Centre; Szeged, Hungary.
authors.forename: Istvan
authors.initials: I
authors.lastname: Krizbai
authors.affiliation: Institute of Biophysics; Biological Research Centre; Szeged, Hungary.
authors.forename: Imola
authors.initials: I
authors.lastname: Wilhelm
authors.affiliation: Paracelsus Medical University; Spinal Cord Injury and Tissue Regeneration Center Salzburg; Institute of Tendon and Bone Regeneration; Salzburg, Austria ; Austrian Cluster for Tissue Regeneration; Vienna, Austria ; University of Salzburg; Department of Organismic Biology; Salzburg, Austria.
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Bauer
authors.affiliation: Paracelsus Medical University; Spinal Cord Injury and Tissue Regeneration Center Salzburg; Institute of Tendon and Bone Regeneration; Salzburg, Austria ; University of Salzburg; Department of Organismic Biology; Salzburg, Austria.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Bauer
keywords: PDZ scaffold; ZO-2; cytoprotection; nuclear shuttling; stress response; tight junction