Molecular basis for leukocyte integrin α(E)β7 adhesion to epithelial (E)-cadherin

Karen S. Taraszka, Jonathan M.G. Higgins, Kemin Tan, Didier A. Mandelbrot, Jia Huai Wang, Michael B. Brenner

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Cadherins are expressed in tissue-restricted patterns and typically mediate homophilic adhesion. Cadherins also mediate lymphocyte adhesion, providing the opportunity for lymphocyte attachment to parenchymal cells. The best characterized example of lymphocyte adhesion to a tissue-specific cell adhesion molecule, as opposed to a vascular endothelial adhesion molecule, is the interaction between integrin α(E)β7 on intraepithelial lymphocytes and E-cadherin on epithelial cells. However, the molecular basis for an integrin- cadherin interaction is not well defined. Realization that the cadherin domain adopts a topology similar to the immunoglobulin (Ig) fold suggested that integrin recognition of E-cadherin might be similar to recognition of Ig superfamily ligands. Thus, we modeled domain 1 of human E-cadherin and studied the role of solvent-exposed loops that connect Ig-like core-forming β strands. Mutational analyses localized the integrin α(E)β7 recognition site to the top of domain 1 at the face formed by the BC and FG loops, a site distinct from the region recognized in intercellular adhesion molecule (ICAM)-1, -2, and -3, mucosal addressin cell adhesion molecule 1 (MAdCAM-1), vascular cell adhesion molecule 1 (VCAM-1), and fibronectin by their integrin ligands. Moreover, the integrin α(E)β7 binding site is distinct from the homophilic binding site on E-cadherin. These studies provide a conceptual basis for integrin-cadherin binding and extend the model that an Ig-like fold can serve as a scaffold for recognition.

Original languageEnglish (US)
Pages (from-to)1555-1567
Number of pages13
JournalJournal of Experimental Medicine
Volume191
Issue number9
DOIs
StatePublished - May 1 2000

Keywords

  • Cadherins
  • Cell adhesion
  • Integrins
  • Protein binding
  • T lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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