Rap1 regulates the formation of E-cadherin-based cell-cell contacts

Mol Cell Biol. 2004 Aug;24(15):6690-700. doi: 10.1128/MCB.24.15.6690-6700.2004.


In epithelial tissues, cells are linked to their neighbors through specialized cell-cell adhesion proteins. E-cadherin is one of the most important membrane proteins for the establishment of intimate cell-cell contacts, but the molecular mechanism by which it is recruited to contact sites is largely unknown. We report here that the cytoplasmic domain of E-cadherin interacts with C3G, a guanine nucleotide exchange factor for Rap1. In epithelial cell cultures, ligation of the extracellular domain of E-cadherin enhances Rap1 activity, which in turn is necessary for the proper targeting of E-cadherin molecules to maturing cell-cell contacts. Furthermore, our data suggest that Cdc42 functions downstream of Rap1 in this process. We conclude that Rap1 plays a vital role in the establishment of E-cadherin-based cell-cell adhesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Blotting, Western
  • CHO Cells
  • Cadherins / metabolism*
  • Calcium / metabolism
  • Cell Adhesion
  • Cell Communication
  • Cell Line
  • Cell Line, Tumor
  • Cricetinae
  • Cytoplasm / metabolism
  • Epithelium / metabolism
  • Guanine Nucleotide-Releasing Factor 2 / metabolism
  • Guanosine Triphosphate / metabolism
  • Humans
  • Microscopy, Fluorescence
  • Plasmids / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Time Factors
  • Transfection
  • Two-Hybrid System Techniques
  • cdc42 GTP-Binding Protein / metabolism
  • rap1 GTP-Binding Proteins / metabolism*


  • Cadherins
  • Guanine Nucleotide-Releasing Factor 2
  • Guanosine Triphosphate
  • cdc42 GTP-Binding Protein
  • rap1 GTP-Binding Proteins
  • Calcium