Direct and Regulated Interaction of Integrin αEβ7 with E-Cadherin
| Autor: | Didier A. Mandlebrot, W. James Nelson, Elizabeth A. Murphy, Yih-Tai Chen, Sunil K. Shaw, Michael B. Brenner, Christina M. Parker, Gary J. Russell, Jonathan M.G. Higgins |
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| Rok vydání: | 1998 |
| Předmět: |
Models
Molecular Integrins Recombinant Fusion Proteins T-Lymphocytes Genetic Vectors Integrin Biology Transfection Polymerase Chain Reaction CD49c Article Cell Line Collagen receptor Mice 03 medical and health sciences 0302 clinical medicine Cell Adhesion Animals Humans Amino Acid Sequence Intestinal Mucosa Cell adhesion 030304 developmental biology 0303 health sciences Cell adhesion molecule Antibodies Monoclonal Cell Biology Cadherins Molecular biology Immunoglobulin Fc Fragments Cell biology Kinetics Integrin alpha M Immunoglobulin G biology.protein Integrin beta 6 Neural cell adhesion molecule Protein Binding 030215 immunology |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.140.1.197 |
| Popis: | 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, alphaEbeta7, has been proposed. Here, we demonstrate that a human E-cadherin-Fc fusion protein binds directly to soluble recombinant alphaEbeta7, and to alphaEbeta7 solubilized from intraepithelial T lymphocytes. Furthermore, intraepithelial lymphocytes or transfected JY' cells expressing the alphaEbeta7 integrin adhere strongly to purified E-cadherin-Fc coated on plastic, and the adhesion can be inhibited by antibodies to alphaEbeta7 or E-cadherin. The binding of alphaEbeta7 integrin to cadherins is selective since cell adhesion to P-cadherin-Fc through alphaEbeta7 requires100-fold more fusion protein than to E-cadherin-Fc. Although the structure of the alphaE-chain is unique among integrins, the avidity of alphaEbeta7 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 alphaEbeta7 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 alphaEbeta7 integrin. |
| Databáze: | OpenAIRE |
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