Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation.
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.
Bax
Daniel V
DV
UK Centre for Tissue Engineering, University of Manchester, Manchester, M13 9PT, UK.
Mahalingam
Yashithra
Y
Cain
Stuart
S
Mellody
Kieran
K
Freeman
Lyle
L
Younger
Kerri
K
Shuttleworth
C Adrian
CA
Humphries
Martin J
MJ
Couchman
John R
JR
Kielty
Cay M
CM
D001483:Base Sequence; D001665:Binding Sites; D002448:Cell Adhesion; D017931:DNA Primers; D004815:Epidermal Growth Factor / Q000378:metabolism; D000071838:Fibrillin-1; D000071837:Fibrillins; D006493:Heparin / Q000378:metabolism*; D039081:Integrin alpha5beta1 / Q000502:physiology; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009842:Oligopeptides / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054392:Adipokines
D017931:DNA Primers; D004815:Epidermal Growth Factor; D000071838:Fibrillin-1; D000071837:Fibrillins; D006493:Heparin; D039081:Integrin alpha5beta1; D008840:Microfilament Proteins; D009842:Oligopeptides; D011994:Recombinant Proteins; C000605722:FBN1 protein, human; D054392:Adipokines; C047981:arginyl-glycyl-aspartic acid