Zyxin controls migration in epithelial-mesenchymal transition by mediating actin-membrane linkages at cell-cell junctions

J Cell Physiol. 2010 Mar;222(3):612-24. doi: 10.1002/jcp.21977.

Abstract

Development is punctuated by morphogenetic rearrangements of epithelial tissues, including detachment of motile cells during epithelial-mesenchymal transition (EMT). Dramatic actin rearrangements occur as cell-cell junctions are dismantled and cells become independently motile during EMT. Characterizing dynamic actin rearrangements and identifying actin machinery driving these rearrangements is essential for understanding basic mechanisms of cell-cell junction remodeling. Using immunofluorescence and live cell imaging of scattering MDCK cells we examine dynamic actin rearrangement events during EMT and demonstrate that zyxin-VASP complexes mediate linkage of dynamic medial actin networks to adherens junction (AJ) membranes. A functional analysis of zyxin in EMT reveals its role in regulating disruption of actin membrane linkages at cell-cell junctions, altering cells' ability to fully detach and migrate independently during EMT. Expression of a constitutively active zyxin mutant results in persistent actin-membrane linkages and cell migration without loss of cell-cell adhesion. We propose zyxin functions in morphogenetic rearrangements, maintaining collective migration by transducing individual cells' movements through AJs, thus preventing the dissociation of individual migratory cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Adherens Junctions / metabolism*
  • Animals
  • Cell Adhesion
  • Cell Adhesion Molecules / metabolism
  • Cell Line
  • Cell Movement*
  • Cell Shape
  • Cell Transdifferentiation*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Dogs
  • Epithelial Cells / metabolism*
  • Fluorescent Antibody Technique
  • Hepatocyte Growth Factor / metabolism
  • Mesoderm / cytology
  • Mesoderm / metabolism*
  • Microfilament Proteins / metabolism
  • Microscopy, Fluorescence
  • Microscopy, Video
  • Mutation
  • Phosphoproteins / metabolism
  • RNA Interference
  • Time Factors

Substances

  • Actins
  • Cell Adhesion Molecules
  • Cytoskeletal Proteins
  • Microfilament Proteins
  • Phosphoproteins
  • vasodilator-stimulated phosphoprotein
  • Hepatocyte Growth Factor