Rap1 regulates the formation of E-cadherin-based cell-cell contacts.
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.
Hogan
Catherine
C
MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, Gower Street, London WC1E 6BT, United Kingdom.
Serpente
Norberto
N
Cogram
Patricia
P
Hosking
Catherine Rose
CR
Bialucha
Carl Uli
CU
Feller
Stephan Michael
SM
Braga
Vania M M
VM
Birchmeier
Walter
W
Fujita
Yasuyuki
Y
D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D016466:CHO Cells; D015820:Cadherins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D002450:Cell Communication; D002460:Cell Line; D045744:Cell Line, Tumor; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D020735:Guanine Nucleotide-Releasing Factor 2 / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013997:Time Factors; D014162:Transfection; D020798:Two-Hybrid System Techniques; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*
D015820:Cadherins; D020735:Guanine Nucleotide-Releasing Factor 2; D006160:Guanosine Triphosphate; D020764:cdc42 GTP-Binding Protein; D020827:rap1 GTP-Binding Proteins; D002118:Calcium