Journal article
EWI-2 regulates α3β1 integrin–dependent cell functions on laminin-5
The Journal of Cell Biology, Vol.163(5), pp.1167-1177
12/08/2003
DOI: 10.1083/jcb.200309113
PMCID: PMC2173626
PMID: 14662754
Abstract
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.
Details
- Title: Subtitle
- EWI-2 regulates α3β1 integrin–dependent cell functions on laminin-5
- Creators
- Christopher S Stipp - Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115Tatiana V Kolesnikova - Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115Martin E Hemler - Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115
- Resource Type
- Journal article
- Publication Details
- The Journal of Cell Biology, Vol.163(5), pp.1167-1177
- Publisher
- The Rockefeller University Press
- DOI
- 10.1083/jcb.200309113
- PMID
- 14662754
- PMCID
- PMC2173626
- ISSN
- 0021-9525
- eISSN
- 1540-8140
- Language
- English
- Date published
- 12/08/2003
- Academic Unit
- Molecular Physiology and Biophysics; Biology
- Record Identifier
- 9983991989502771
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