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

Abstract

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.

We thank Alan Hall and Martin Raff (London) for critical reading of the manuscript. Sabine Wilhelm (Berlin) is acknowledged for technical help. We also thank Andrew Vaughan (London) for help with microscopic analysis, Julien Cau (London) for help with Metamorph software, Johannes L. Bos (Utrecht, The Netherlands) for providing various Rap constructs, Albert B. Reynolds (Nashville, Tenn.) for the pBS-p120^ctn construct, Claire Wells and Gareth Jones (London) for the pGEX-WASP-CRIB construct, and Carien Niessen (Cologne, Germany) for providing stably transfected CHO cells expressing hE/Fc.

V.M.M.B. is an MRC Senior Research Fellow.