Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation.

Research output: Contribution to journalJournal articleResearchpeer-review

Daniel V Bax, Yashithra Mahalingam, Stuart Cain, Kieran Mellody, Lyle Freeman, Kerri Younger, C Adrian Shuttleworth, Martin J Humphries, John R Couchman, Cay M Kielty

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-alpha(5)beta(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.
Original languageEnglish
JournalJournal of Cell Science
Volume120
Issue numberPt 8
Pages (from-to)1383-92
Number of pages9
ISSN0021-9533
DOIs
Publication statusPublished - 2007

Bibliographical note

Keywords: Base Sequence; Binding Sites; Cell Adhesion; DNA Primers; Epidermal Growth Factor; Heparin; Integrin alpha5beta1; Microfilament Proteins; Mutagenesis, Site-Directed; Oligopeptides; Recombinant Proteins

ID: 5160728