Direct and regulated interaction of integrin alphaEbeta7 with E-cadherin

Area of Science:

• Cell adhesion molecules
• Immunology
• Integrin biology

Background:

• Cadherins mediate cell-cell adhesion and tissue formation.
• Integrins bind to immunoglobulin superfamily molecules.
• A potential interaction between E-cadherin and alphaEbeta7 integrin was proposed.

Purpose of the Study:

• To investigate the direct interaction between E-cadherin and alphaEbeta7 integrin.
• To characterize the binding specificity and regulation of this interaction.

Main Methods:

• Binding assays using E-cadherin-Fc fusion protein and recombinant/solubilized alphaEbeta7.
• Cell adhesion assays with intraepithelial lymphocytes or transfected cells expressing alphaEbeta7.
• Inhibition studies using antibodies against alphaEbeta7 or E-cadherin.
• Selectivity assays comparing E-cadherin and P-cadherin binding.
• Avidity regulation studies using divalent cations, phorbol myristate acetate, and T cell receptor cross-linking.

Main Results:

• E-cadherin-Fc fusion protein directly binds to alphaEbeta7.
• AlphaEbeta7-expressing cells adhere strongly to E-cadherin.
• Antibodies to alphaEbeta7 or E-cadherin inhibit this adhesion.
• Binding is selective for E-cadherin over P-cadherin.
• AlphaEbeta7 avidity for E-cadherin is regulated by cations, PMA, and T cell receptor activation.

Conclusions:

• E-cadherin is a direct counter-receptor for the alphaEbeta7 integrin.
• This interaction plays a role in lymphocyte adherence and activation within the epithelium.
• The findings reveal a novel ligand for alphaEbeta7, distinct from known integrin ligands.