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Molecular and Cellular Biology, August 2004, p. 6690-6700, Vol. 24, No. 15
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.15.6690-6700.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Rap1 Regulates the Formation of E-Cadherin-Based Cell-Cell Contacts

Catherine Hogan,1 Norberto Serpente,1 Patricia Cogram,1 Catherine Rose Hosking,1 Carl Uli Bialucha,1 Stephan Michael Feller,2 Vania M. M. Braga,3 Walter Birchmeier,4 and Yasuyuki Fujita1*

MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, and Department of Biology, University College London, London WC1E 6BT,1 Cancer Research UK Cell Signalling Group, Weatherall Institute of Molecular Medicine, Oxford OX3 9DS,2 Cell and Molecular Biology Section, Division of Biomedical Sciences, Imperial College School of Medicine, London SW7 2AZ, United Kingdom,3 Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany4

Received 16 December 2003/ Returned for modification 28 January 2004/ Accepted 11 May 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.

* 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: y.fujita{at}ucl.ac.uk.

Molecular and Cellular Biology, August 2004, p. 6690-6700, Vol. 24, No. 15
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.15.6690-6700.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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