PT  - JOURNAL ARTICLE
AU  - Bax, Daniel V.
AU  - Mahalingam, Yashithra
AU  - Cain, Stuart
AU  - Mellody, Kieran
AU  - Freeman, Lyle
AU  - Younger, Kerri
AU  - Shuttleworth, C. Adrian
AU  - Humphries, Martin J.
AU  - Couchman, John R.
AU  - Kielty, Cay M.
TI  - Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation
AID  - 10.1242/jcs.003954
DP  - 2007 Apr 15
TA  - Journal of Cell Science
PG  - 1383--1392
VI  - 120
IP  - 8
4099  - http://jcs.biologists.org/content/120/8/1383.short
4100  - http://jcs.biologists.org/content/120/8/1383.full
SO  - J. Cell Sci.2007 Apr 15; 120
AB  - 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-α5β1-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.