| CD81 regulates cell migration through its association with Rac GTPase. | |
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MedLine Citation:
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PMID: 23264468 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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CD81 is a member of the tetraspanin family that has been described to have a key role in cell migration of tumor and immune cells. To unravel the mechanisms of CD81-regulated cell migration, we performed proteomic analyses that revealed an interaction of the tetraspanin C-terminal domain with the small GTPase Rac. Direct interaction was confirmed biochemically. Moreover, microscopy cross-correlation analysis demonstrated the in situ integration of both molecules into the same molecular complex. Pull-down experiments revealed that CD81-Rac interaction was direct and independent of Rac activation status. Knockdown of CD81 resulted in enhanced protrusion rate, altered focal adhesion formation and decreased cell migration, correlating with increased active Rac. Re-expression of wild type CD81, but not its truncated form lacking the C-terminal cytoplasmic domain, rescued these effects. The phenotype of CD81 knockdown cells was mimicked by treatment with a soluble peptide with the C-terminal sequence of the tetraspanin. Our data show that the interaction of Rac with the C-terminal cytoplasmic domain of CD81 is a novel regulatory mechanism of the GTPase activity turnover. Furthermore, they provide a novel mechanism for tetraspanin-dependent regulation of cell motility and open new avenues for tetraspanin-targeted reagents by the use of cell permeable peptides. |
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Authors:
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Emilio Tejera; Vera Rocha-Perugini; Soraya López-Martín; Daniel Pérez-Hernández; Alexia I Bachir; Alan Rick Horwitz; Jesús Vázquez; Francisco Sánchez-Madrid; María Yáñez-Mo |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-12-21 |
Journal Detail:
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Title: Molecular biology of the cell Volume: - ISSN: 1939-4586 ISO Abbreviation: Mol. Biol. Cell Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9201390 Medline TA: Mol Biol Cell Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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†Unidad de Investigación, Hospital Santa Cristina, Instituto de Investigación Sanitaria La Princesa, Madrid, Spain £Servicio de Inmunología, Hospital de la Princesa, Instituto de Investigación Sanitaria La Princesa, Madrid, Spain $Departamento de Biología Vascular e Inflamación, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain. *Cardiovascular Proteomics Laboratory, Centro de Biología Molecular "Severo Ochoa"-Consejo Superior de Investigaciones Científicas, 28049 Cantoblanco, Madrid, Spain. #Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA 22908. |
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