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EWI-2 regulates α3β1 integrin–dependent cell functions on laminin-5
EWI-2, a cell surface immunoglobulin SF protein of unknown function, associates with tetraspanins CD9 and CD81 with high stoichiometry. Overexpression of EWI-2 in A431 epidermoid carcinoma cells did not alter cell adhesion or spreading on laminin-5, and had no effect on reaggregation of cells plated...
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2003
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173626/ https://www.ncbi.nlm.nih.gov/pubmed/14662754 http://dx.doi.org/10.1083/jcb.200309113 |
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author | Stipp, Christopher S. Kolesnikova, Tatiana V. Hemler, Martin E. |
author_facet | Stipp, Christopher S. Kolesnikova, Tatiana V. Hemler, Martin E. |
author_sort | Stipp, Christopher S. |
collection | PubMed |
description | EWI-2, a cell surface immunoglobulin SF protein of unknown function, associates with tetraspanins CD9 and CD81 with high stoichiometry. Overexpression of EWI-2 in A431 epidermoid carcinoma cells did not alter cell adhesion or spreading on laminin-5, and had no effect on reaggregation of cells plated on collagen I (α2β1 integrin ligand). However, on laminin-5 (α3β1 integrin ligand), A431 cell reaggregation and motility functions were markedly impaired. Immunodepletion and reexpression experiments revealed that tetraspanins CD9 and CD81 physically link EWI-2 to α3β1 integrin, but not to other integrins. CD81 also controlled EWI-2 maturation and cell surface localization. EWI-2 overexpression not only suppressed cell migration, but also redirected CD81 to cell filopodia and enhanced α3β1–CD81 complex formation. In contrast, an EWI-2 chimeric mutant failed to suppress cell migration, redirect CD81 to filopodia, or enhance α3β1–CD81 complex formation. These results show how laterally associated EWI-2 might regulate α3β1 function in disease and development, and demonstrate how tetraspanin proteins can assemble multiple nontetraspanin proteins into functional complexes. |
format | Text |
id | pubmed-2173626 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21736262008-05-01 EWI-2 regulates α3β1 integrin–dependent cell functions on laminin-5 Stipp, Christopher S. Kolesnikova, Tatiana V. Hemler, Martin E. J Cell Biol Article EWI-2, a cell surface immunoglobulin SF protein of unknown function, associates with tetraspanins CD9 and CD81 with high stoichiometry. Overexpression of EWI-2 in A431 epidermoid carcinoma cells did not alter cell adhesion or spreading on laminin-5, and had no effect on reaggregation of cells plated on collagen I (α2β1 integrin ligand). However, on laminin-5 (α3β1 integrin ligand), A431 cell reaggregation and motility functions were markedly impaired. Immunodepletion and reexpression experiments revealed that tetraspanins CD9 and CD81 physically link EWI-2 to α3β1 integrin, but not to other integrins. CD81 also controlled EWI-2 maturation and cell surface localization. EWI-2 overexpression not only suppressed cell migration, but also redirected CD81 to cell filopodia and enhanced α3β1–CD81 complex formation. In contrast, an EWI-2 chimeric mutant failed to suppress cell migration, redirect CD81 to filopodia, or enhance α3β1–CD81 complex formation. These results show how laterally associated EWI-2 might regulate α3β1 function in disease and development, and demonstrate how tetraspanin proteins can assemble multiple nontetraspanin proteins into functional complexes. The Rockefeller University Press 2003-12-08 /pmc/articles/PMC2173626/ /pubmed/14662754 http://dx.doi.org/10.1083/jcb.200309113 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Stipp, Christopher S. Kolesnikova, Tatiana V. Hemler, Martin E. EWI-2 regulates α3β1 integrin–dependent cell functions on laminin-5 |
title | EWI-2 regulates α3β1 integrin–dependent cell functions on laminin-5 |
title_full | EWI-2 regulates α3β1 integrin–dependent cell functions on laminin-5 |
title_fullStr | EWI-2 regulates α3β1 integrin–dependent cell functions on laminin-5 |
title_full_unstemmed | EWI-2 regulates α3β1 integrin–dependent cell functions on laminin-5 |
title_short | EWI-2 regulates α3β1 integrin–dependent cell functions on laminin-5 |
title_sort | ewi-2 regulates α3β1 integrin–dependent cell functions on laminin-5 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173626/ https://www.ncbi.nlm.nih.gov/pubmed/14662754 http://dx.doi.org/10.1083/jcb.200309113 |
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