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PMID: 14662754 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

EWI-2 regulates alpha3beta1 integrin-dependent cell functions on laminin-5.

The Journal of cell biology ·Vol. 163 ·No. 5 ·2003-12-08 ·Pages 1167-77

Stipp CS, Kolesnikova TV, Hemler ME

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 (alpha2beta1 integrin ligand). However, on laminin-5 (alpha3beta1 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 alpha3beta1 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 alpha3beta1-CD81 complex formation. In contrast, an EWI-2 chimeric mutant failed to suppress cell migration, redirect CD81 to filopodia, or enhance alpha3beta1-CD81 complex formation. These results show how laterally associated EWI-2 might regulate alpha3beta1 function in disease and development, and demonstrate how tetraspanin proteins can assemble multiple nontetraspanin proteins into functional complexes.

MeSH Terms
Animals Antigens, CD/metabolism CD2 Antigens/metabolism Cell Adhesion Molecules/metabolism Cell Line, Tumor Cell Movement/physiology Humans Immunoglobulins/metabolism Integrin alpha3beta1/metabolism Macromolecular Substances Membrane Glycoproteins/metabolism Membrane Proteins/metabolism Recombinant Fusion Proteins/genetics,metabolism Tetraspanin 28 Tetraspanin 29
Chemicals
Antigens, CD CD2 Antigens CD81 protein, human CD9 protein, human Cell Adhesion Molecules IGSF8 protein, human Immunoglobulins Integrin alpha3beta1 Macromolecular Substances Membrane Glycoproteins Membrane Proteins Recombinant Fusion Proteins Tetraspanin 28 Tetraspanin 29 kalinin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Stipp Christopher S
Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Kolesnikova Tatiana V
Hemler Martin E
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200309113
Published
2003-12-08
Pages
1167-77
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2173626
Subset
IM
Grants
NCI NIH HHS · R01 CA042368 · United States
NIGMS NIH HHS · R01 GM038903 · United States
NCI NIH HHS · CA42368 · United States
NIGMS NIH HHS · GM38903 · United States
External Links
PubMed source DOI: 10.1083/jcb.200309113 PMC Full Text View journal details
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