Interaction between Erbin and a Catenin-related protein in epithelial cells

J Biol Chem. 2002 Jan 25;277(4):2869-75. doi: 10.1074/jbc.M109652200. Epub 2001 Nov 15.

Abstract

Integrity of epithelial tissues relies on the proper apical-basolateral polarity of epithelial cells. Members of the LAP (LRR and PDZ) protein family such as LET-413 and Scribble are involved in maintaining epithelial cell polarity in Caenorhabditis elegans and Drosophila melanogaster, respectively. We previously described Erbin as a mammalian LET-413 homologue interacting with ERBB2/HER2, an epidermal growth factor receptor family member. Erbin and ERBB2/HER2 are located in the basolateral membranes of epithelial cells. We show here that Erbin interacts with p0071 (also called plakophilin-4), an armadillo repeat protein linked to the cytoskeleton. Erbin binds to p0071 in vitro and in vivo in a PDZ domain-dependent manner, and both proteins colocalized in desmosomes of epithelial cells. Using a dominant negative approach, we found that integrity of epithelial cell monolayer is impaired when interaction between Erbin and p0071 is disrupted. We propose that Erbin is connected by p0071 to cytoskeletal networks in an interaction crucial for epithelial homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Biotinylation
  • COS Cells
  • Caco-2 Cells
  • Cadherins / metabolism*
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cell Membrane / metabolism
  • Cytoskeletal Proteins / biosynthesis
  • Cytoskeletal Proteins / chemistry*
  • Cytoskeletal Proteins / metabolism*
  • Cytoskeleton / metabolism
  • DNA / metabolism
  • Desmosomes / metabolism
  • Dogs
  • Epithelial Cells / metabolism*
  • Genes, Dominant
  • HeLa Cells
  • Humans
  • Kinetics
  • Ligands
  • Microscopy, Immunoelectron
  • Molecular Sequence Data
  • Plakophilins
  • Protein Binding
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Surface Plasmon Resonance
  • Time Factors
  • Two-Hybrid System Techniques

Substances

  • Adaptor Proteins, Signal Transducing
  • Cadherins
  • Carrier Proteins
  • Cytoskeletal Proteins
  • ERBIN protein, human
  • Ligands
  • PKP4 protein, human
  • Plakophilins
  • Recombinant Fusion Proteins
  • DNA