Cell Adhesion to Fibrillin-1 Molecules and Microfibrils Is Mediated by α5β1 and αvβ3 Integrins*

By D. Bax, Sarah E. Bernard, A. Lomas, A. Morgan, J. Humphries, C. Shuttleworth, M. J. Humphries, C. Kielty. Journal of Biological Chemistry, 2003

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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 α5β1 interactions with fibrillin ligands were identified, but integrin αvβ3 also contributed to cell adhesion. Fluorescence-activated cell sorting analysis confirmed the presence of abundant α5β1 and some αvβ3 receptors on these cells. Adhesion to microfibrils and to Arg-Gly-Aspcontaining 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 α5β1-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 β1 integrin activation. A375-SM melanoma cells bound Arg-Gly-Asp-containing fibrillin-1 protein fragments mainly through αvβ3, whereas HT1080 cells used mainly α5β1. This study has shown that fibrillin microfibrils mediate cell adhesion, that α5β1 and αvβ3 are both important but cell-specific fibrillin-1 receptors, and that cellular interactions with fibrillin-1 influence cell behavior.

Subfields: Cancer Research, Genetics, Immunology and Allergy

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