title: Heparin/heparan sulfate controls fibrillin-1, -2 and -3 self-interactions in microfibril assembly.
abstract: Fibrillins form multifunctional microfibrils in most connective tissues. Deficiencies in fibrillin assembly can result in fibrillinopathies, such as Marfan syndrome. We demonstrate the presence of heparin/heparan sulfate binding sites in fibrillin-2 and -3. Multimerization of all three fibrillins drastically increased the apparent affinity of their interaction with heparin/heparan sulfate. Surprisingly, contrary to other reports heparin/heparan sulfate strongly inhibited homo- and heterotypic N-to-C-terminal fibrillin interactions. These data suggest that heparin/heparan sulfate controls the formation of microfibrils at the bead interaction stage.
authors.affiliation: Faculty of Medicine, Department of Anatomy and Cell Biology, McGill University, Montreal, QC H3A 0C7, Canada.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Sabatier
authors.affiliation: Faculty of Medicine, Department of Anatomy and Cell Biology, McGill University, Montreal, QC H3A 0C7, Canada.
authors.forename: Jelena
authors.initials: J
authors.lastname: Djokic
authors.affiliation: Faculty of Medicine, Department of Anatomy and Cell Biology, McGill University, Montreal, QC H3A 0C7, Canada.
authors.forename: Dirk
authors.initials: D
authors.lastname: Hubmacher
authors.affiliation: Faculty of Medicine, Department of Anatomy and Cell Biology, McGill University, Montreal, QC H3A 0C7, Canada.
authors.forename: Dzaner
authors.initials: D
authors.lastname: Dzafik
authors.affiliation: Faculty of Dentistry, McGill University, Montreal, QC H3A 0C7, Canada.
authors.forename: Valentin
authors.initials: V
authors.lastname: Nelea
authors.affiliation: Faculty of Medicine, Department of Anatomy and Cell Biology, McGill University, Montreal, QC H3A 0C7, Canada; Faculty of Dentistry, McGill University, Montreal, QC H3A 0C7, Canada. Electronic address: dieter.reinhardt@mcgill.ca.
authors.forename: Dieter P
authors.initials: DP
authors.lastname: Reinhardt
mesh_terms: D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D020894:Microfibrils / Q000187:drug effects / Q000378:metabolism*; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D006493:Heparin; D006497:Heparan Sulfate; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines; C000605723:FBN2 protein, human; C493782:FBN3 protein, human
keywords: Assembly; Connective tissue; Extracellular matrix; Fibrillin; Fibronectin; Heparan sulfate; Microfibrils