The tight junction protein, occludin, regulates the directional migration of epithelial cells

Dev Cell. 2010 Jan 19;18(1):52-63. doi: 10.1016/j.devcel.2009.12.008.

Abstract

Cell polarity proteins regulate tight junction formation and directional migration in epithelial cells. To date, the mechanism by which these polarity proteins assemble at the leading edge of migrating epithelial cells remains unclear. We report that occludin, a transmembrane protein, is localized at the leading edge of migrating cells and regulates directional cell migration. During migration, occludin knockdown disrupted accumulation of aPKC-Par3 and PATJ at the leading edge, and led to a disorganized microtubule network and defective reorientation of the microtubule organization center (MTOC). Phosphorylation of occludin at tyrosine 473 residue allowed recruitment of p85 alpha to the leading edge via association with its C-terminal SH2 domain. Loss of occludin attenuated activation of PI3K, leading to disorganization of the actin cytoskeleton and reduced cell protrusions. Our data indicate that occludin is required for the leading-edge localization of polarity proteins aPKC-Par3 and PATJ and promotes cell protrusion by regulating membrane-localized activation of PI3K.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / ultrastructure
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Cell Adhesion Molecules / metabolism
  • Cell Cycle Proteins
  • Cell Line
  • Cell Movement / physiology*
  • Cell Polarity / physiology*
  • Cell Surface Extensions / physiology
  • Dogs
  • Down-Regulation / genetics
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Extracellular Matrix Proteins / metabolism
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microtubules / metabolism
  • Microtubules / pathology
  • Occludin
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Protein Kinase C / metabolism
  • Protein Structure, Tertiary / physiology
  • Signal Transduction / physiology
  • Tight Junction Proteins
  • Tight Junctions / metabolism*
  • Tight Junctions / ultrastructure

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Adhesion Molecules
  • Cell Cycle Proteins
  • Ecm1 protein, mouse
  • Extracellular Matrix Proteins
  • Membrane Proteins
  • OCLN protein, human
  • Occludin
  • Ocln protein, mouse
  • PATJ protein, human
  • Pard3 protein, mouse
  • Tight Junction Proteins
  • PKC-3 protein
  • Protein Kinase C