Molecular basis for leukocyte integrin αEβ7 adhesion to epithelial (E)-cadherin

被引:48
作者
Taraszka, KS
Higgins, JMG
Tan, KM
Mandelbrot, DA
Wang, JH
Brenner, MB
机构
[1] Brigham & Womens Hosp, Dept Internal Med, Div Rheumatol Allergy & Immunol, Lymphocyte Biol Sect, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA
基金
英国惠康基金;
关键词
cadherins; integrins; cell adhesion; T lymphocytes; protein binding;
D O I
10.1084/jem.191.9.1555
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 alpha(E)beta(7) 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 beta strands. Mutational analyses localized the integrin alpha(E)beta(7) 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 alpha(E)beta(7) 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.
引用
收藏
页码:1555 / 1567
页数:13
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