title: Fibrillin-1 and -2 contain heparin-binding sites important for matrix deposition and that support cell attachment.
abstract: Fibrillin-1 and -2 are large modular extracellular matrix glycoproteins found in many vertebrate organ systems and are known to be key components of the elastic fibre. In the present study, we identify a new heparin-binding region in fibrillin-2 between exons 18 and 24. Additionally, we have narrowed the location of heparin-binding activity previously identified in fibrillin-1 to the last 17 residues of the mature proteolytically processed protein. This domain demonstrated higher activity as a multimer than as a monomer. The fibrillin-1 C-terminal site supported cell attachment in each of nine cell types tested. Attachment was shown to be mediated by cell-surface heparan sulphate proteoglycans. Fibrillin-1 has been shown previously to have heparin-binding activity that is important for matrix deposition of the molecule by fibroblasts. This function in deposition was confirmed in two additional fibrillin-producing cell types (osteosarcoma and epithelial cells) for the deposition of both fibrillin-1 and -2 into the extracellular matrix.
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Ritty
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Broekelmann
authors.forename: Claudio C
authors.initials: CC
authors.lastname: Werneck
authors.forename: Robert P
authors.initials: RP
authors.lastname: Mecham
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D016466:CHO Cells; D019556:COS Cells; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006224:Cricetinae; D019281:Dimerization; D004847:Epithelial Cells / Q000166:cytology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D006025:Glycosaminoglycans / Q000494:pharmacology; D006493:Heparin / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D012516:Osteosarcoma / Q000473:pathology; D011509:Proteoglycans / Q000494:pharmacology; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D006025:Glycosaminoglycans; D006493:Heparin; D008840:Microfilament Proteins; D011509:Proteoglycans; C000605722:FBN1 protein, human; D054392:Adipokines; C000605723:FBN2 protein, human; C000605724:Fbn1 protein, mouse; C000605728:Fbn2 protein, mouse