Cell adhesion to fibrillin-1 molecules and microfibrils is mediated by alpha 5 beta 1 and alpha v beta 3 integrins
| Autor: | Daniel V, Bax, Sarah E, Bernard, Amanda, Lomas, Amanda, Morgan, Jon, Humphries, C Adrian, Shuttleworth, Martin J, Humphries, Cay M, Kielty |
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| Rok vydání: | 2003 |
| Předmět: |
Integrins
Fibrillin-1 Cell Separation Fibrillins Ligands Models Biological Antibodies Cations Cell Adhesion Tumor Cells Cultured Humans Cells Cultured Cytoskeleton Dose-Response Relationship Drug Microfilament Proteins Muscle Smooth Exons Fibroblasts Flow Cytometry Integrin alphaVbeta3 Recombinant Proteins Protein Structure Tertiary Phenotype Microscopy Fluorescence Microfibrils Electrophoresis Polyacrylamide Gel Integrin alpha5beta1 Protein Binding Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 278(36) |
| ISSN: | 0021-9258 |
| Popis: | Fibrillins are the major glycoprotein components of microfibrils that form a template for tropoelastin during elastic fibrillogenesis. We have examined cell adhesion to assembled purified microfibrils, and its molecular basis. Human dermal fibroblasts exhibited Arg-Gly-Asp and cation-dependent adhesion to microfibrils and recombinant fibrillin-1 protein fragments. Strong integrin alpha 5 beta 1 interactions with fibrillin ligands were identified, but integrin alpha v beta 3 also contributed to cell adhesion. Fluorescence-activated cell sorting analysis confirmed the presence of abundant alpha 5 beta 1 and some alpha v beta 3 receptors on these cells. Adhesion to microfibrils and to Arg-Gly-Asp containing fibrillin-1 protein fragments induced signaling events that led to cell spreading, altered cytoskeletal organization, and enhanced extracellular fibrillin-1 deposition. Differences in cell shape when plated on fibrillin or fibronectin implied substrate-specific alpha 5 beta 1-mediated cellular responses. An Arg-Gly-Asp-independent cell adhesion sequence was also identified within fibrillin-1. Adhesion and spreading of smooth muscle cells on fibrillin ligands was enhanced by antibody-induced beta1 integrin activation. A375-SM melanoma cells bound Arg-Gly-Asp-containing fibrillin-1 protein fragments mainly through alpha v beta 3, whereas HT1080 cells used mainly alpha 5 beta 1. This study has shown that fibrillin microfibrils mediate cell adhesion, that alpha 5 beta 1 and alpha v beta 3 are both important but cell-specific fibrillin-1 receptors, and that cellular interactions with fibrillin-1 influence cell behavior. |
| Databáze: | OpenAIRE |
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