Recognition of E-cadherin by integrin alpha(E)beta(7): requirement for cadherin dimerization and implications for cadherin and integrin function.
We have investigated the importance of dimerization of E-cadherin in the heterophilic adhesive interaction between E-cadherin and integrin alpha(E)beta(7). Dimerization of cadherin molecules in parallel alignment is known to be essential for homophilic adhesion and has been attributed to Ca(2+)-dependent interactions in the domain 1-2 junction or to cross-intercalation of Trp2 from one molecule to the other. We have disrupted either or both of these proposed mechanisms by point mutations in E-cadherin-Fc and have tested the modified proteins for alpha(E)beta(7)-mediated cell adhesion. Prevention of Trp2 intercalation had no adverse effect on integrin-mediated adhesion, whereas disruption of Ca(2+) binding permitted adhesion but with reduced efficiency. Both modifications in combination abolished recognition by alpha(E)beta(7). In EGTA, alpha(E)beta(7) adhered to wild type E-cadherin but not to the Trp2 deletion mutant. Independent evidence that the mutations prevented either or both mechanisms for dimerization is presented. The data show that dimerization is required for recognition by alpha(E)beta(7) and that it can take place by either of two mechanisms. Implications for the roles of the alpha(E) and beta(7) integrin subunits in ligand binding and for Trp2 and Ca(2+) in the assembly of cadherin complexes are discussed.
Corps
E
E
Molecular Immunology Programme, The Babraham Institute, Babraham, Cambridge, CB2 4AT, United Kingdom.
Carter
C
C
Karecla
P
P
Ahrens
T
T
Evans
P
P
Kilshaw
P
P
D000818:Animals; D019556:COS Cells; D015820:Cadherins / Q000737:chemistry* / Q000502:physiology; D002118:Calcium / Q000502:physiology; D002448:Cell Adhesion; D019281:Dimerization; D015951:Factor Xa / Q000737:chemistry; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry; D016023:Integrins / Q000737:chemistry* / Q000502:physiology; D011487:Protein Conformation
D015820:Cadherins; D007141:Immunoglobulin Fc Fragments; D016023:Integrins; C070709:integrin alphaEbeta7; D015951:Factor Xa; D002118:Calcium