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First published online 20 March 2007
doi: 10.1242/jcs.003954
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Research Article |
1 UK Centre for Tissue Engineering, Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, UK
2 Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, UK
3 Faculty of Medicine, Imperial College London, Exhibition Road, London, SW7 2AZ, UK
* Author for correspondence (e-mail: cay.kielty{at}manchester.ac.uk)
Accepted 5 February 2007
We have defined the molecular basis of cell adhesion to fibrillin-1, the major structural component of extracellular microfibrils that are associated with elastic fibres. Using human dermal fibroblasts, and recombinant domain swap fragments containing the Arg-Gly-Asp motif, we have demonstrated a requirement for upstream domains for integrin-
5
1-mediated cell adhesion and migration. An adjacent heparin-binding site, which supports focal adhesion formation, was mapped to the fibrillin-1 TB5 motif. Site-directed mutagenesis revealed two arginine residues that are crucial for heparin binding, and confirmed their role in focal adhesion formation. These integrin and syndecan adhesion motifs juxtaposed on fibrillin-1 are evolutionarily conserved and reminiscent of similar functional elements on fibronectin, highlighting their crucial functional importance.
Key words: Fibrillin-1, Cell adhesion, Integrins, Heparin, Syndecan-4, Fibronectin
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