Spatio-temporal regulation of Rac1 localization and lamellipodia dynamics during epithelial cell-cell adhesion

Dev Cell. 2002 Aug;3(2):259-70. doi: 10.1016/s1534-5807(02)00216-2.


Cadherin-dependent epithelial cell-cell adhesion is thought to be regulated by Rho family small GTPases and PI 3-kinase, but the mechanisms involved are poorly understood. Using time-lapse microscopy and quantitative image analysis, we show that cell-cell contact in MDCK epithelial cells coincides with a spatio-temporal reorganization of plasma membrane Rac1 and lamellipodia from noncontacting to contacting surfaces. Within contacts, Rac1 and lamellipodia transiently concentrate at newest sites, but decrease at older, stabilized sites. Significantly, Rac1 mutants alter kinetics of cell-cell adhesion and strengthening, but not the eventual generation of cell-cell contacts. Products of PI 3-kinase activity also accumulate dynamically at contacts, but are not essential for either initiation or development of cell-cell adhesion. These results define a role for Rac1 in regulating the rates of initiation and strengthening of cell-cell adhesion.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism
  • Animals
  • Biological Assay
  • Cell Adhesion / physiology*
  • Cell Communication / physiology*
  • Cell Compartmentation / physiology*
  • Cell Membrane / metabolism*
  • Cell Movement / physiology
  • Enzyme Inhibitors / pharmacology
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Green Fluorescent Proteins
  • Humans
  • Indicators and Reagents
  • Luminescent Proteins
  • Microscopy, Video
  • Mutation / physiology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Pseudopodia / metabolism*
  • Pseudopodia / ultrastructure
  • Time Factors
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism*


  • Actins
  • Enzyme Inhibitors
  • Indicators and Reagents
  • Luminescent Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • Green Fluorescent Proteins
  • rac1 GTP-Binding Protein