title: Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation.
abstract: 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.
authors: UK Centre for Tissue Engineering, University of Manchester, Manchester, M13 9PT, UK.
authors: Daniel V
authors: DV
authors: Bax
authors: Yashithra
authors: Y
authors: Mahalingam
authors: Stuart
authors: S
authors: Cain
authors: Kieran
authors: K
authors: Mellody
authors: Lyle
authors: L
authors: Freeman
authors: Kerri
authors: K
authors: Younger
authors: C Adrian
authors: CA
authors: Shuttleworth
authors: Martin J
authors: MJ
authors: Humphries
authors: John R
authors: JR
authors: Couchman
authors: Cay M
authors: CM
authors: Kielty
mesh_terms: 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
chemical_list: 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