Rap1 Regulates the Formation of E-Cadherin-Based Cell-Cell Contacts
- Catherine Hogan1,
- Norberto Serpente1,
- Patricia Cogram1,
- Catherine Rose Hosking1,
- Carl Uli Bialucha1,
- Stephan Michael Feller2,
- Vania M. M. Braga3,
- Walter Birchmeier4 and
- Yasuyuki Fujita1,*
- 1MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, and Department of Biology, University College London, London WC1E 6BT
- 2Cancer Research UK Cell Signalling Group, Weatherall Institute of Molecular Medicine, Oxford OX3 9DS
- 3Cell and Molecular Biology Section, Division of Biomedical Sciences, Imperial College School of Medicine, London SW7 2AZ, United Kingdom
- 4Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany
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.
- Received 16 December 2003.
- Returned for modification 28 January 2004.
- Accepted 11 May 2004.
- ↵*Corresponding author. Mailing address: MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, Gower Street, London WC1E 6BT, United Kingdom. Phone: 44-20-7679-7208. Fax: 44-20-7679-7805. E-mail: .
- American Society for Microbiology