Direct and regulated interaction of integrin alphaEbeta7 with E-cadherin.
Direct and regulated interaction of integrin alphaEbeta7 with E-cadherin.
复制标题
DOI：
10.1083/jcb.140.1.197
复制
发表时间：
1998-01-12
期刊：
影响因子：
--
通讯作者：
Brenner MB
中科院分区：
文献类型：
--
作者：
Higgins JM;Mandlebrot DA;Shaw SK;Russell GJ;Murphy EA;Chen YT;Nelson WJ;Parker CM;Brenner MB
钙粘蛋白是一类亲同性粘附分子，在细胞连接的形成和组织形态发生中起着至关重要的作用。整合素家族的成员也参与细胞间的粘附，但与免疫球蛋白超家族分子如细胞内粘附分子(ICAM) -1、血管细胞粘附分子(VCAM) -1或粘膜寻址蛋白细胞粘附分子(MadCAM) -1的异源性结合。最近，上皮（E-）钙粘蛋白与粘膜淋巴细胞整合素αEβ7之间的相互作用被提出。在这里，我们证明了人E-cadherin-Fc融合蛋白直接与可溶性重组αEβ7结合，并与上皮内T淋巴细胞溶解的αEβ7结合。此外，上皮内淋巴细胞或转染表达αEβ7整合素的JY细胞与塑料包被的纯化的E-cadherin - fc有很强的粘附，αEβ7或E-cadherin抗体可抑制这种粘附。αEβ7整合素与钙粘蛋白的结合是选择性的，因为细胞通过αEβ7与P-cadherin-Fc的结合需要比E-cadherin-Fc多100倍的融合蛋白。虽然α e链的结构在整合素中是独特的，但α e - β7对e -钙粘蛋白的亲和力可以通过二价阳离子或肉豆蔻酸酯来调节。上皮内淋巴细胞上的T细胞受体复合物的交联增加了α e - β7对e -钙粘蛋白的亲和力，并可能为特异性外来抗原存在时上皮内淋巴细胞的粘附和激活提供了一种机制。因此，尽管它与已知的整合素配体不同，但本文所展示的特定分子相互作用表明，e -钙粘蛋白是αEβ7整合素的直接对抗受体。
The cadherins are a family of homophilic adhesion molecules that play a vital role in the formation of cellular junctions and in tissue morphogenesis. Members of the integrin family are also involved in cell to cell adhesion, but bind heterophilically to immunoglobulin superfamily molecules such as intracellular adhesion molecule (ICAM)–1, vascular cell adhesion molecule (VCAM)–1, or mucosal addressin cell adhesion molecule (MadCAM)–1. Recently, an interaction between epithelial (E-) cadherin and the mucosal lymphocyte integrin, αEβ7, has been proposed. Here, we demonstrate that a human E-cadherin–Fc fusion protein binds directly to soluble recombinant αEβ7, and to αEβ7 solubilized from intraepithelial T lymphocytes. Furthermore, intraepithelial lymphocytes or transfected JY′ cells expressing the αEβ7 integrin adhere strongly to purified E-cadherin–Fc coated on plastic, and the adhesion can be inhibited by antibodies to αEβ7 or E-cadherin. The binding of αEβ7 integrin to cadherins is selective since cell adhesion to P-cadherin–Fc through αEβ7 requires >100-fold more fusion protein than to E-cadherin–Fc. Although the structure of the αE-chain is unique among integrins, the avidity of αEβ7 for E-cadherin can be regulated by divalent cations or phorbol myristate acetate. Cross-linking of the T cell receptor complex on intraepithelial lymphocytes increases the avidity of αEβ7 for E-cadherin, and may provide a mechanism for the adherence and activation of lymphocytes within the epithelium in the presence of specific foreign antigen. Thus, despite its dissimilarity to known integrin ligands, the specific molecular interaction demonstrated here indicates that E-cadherin is a direct counter receptor for the αEβ7 integrin.