title: Cell-type specific recognition of RGD- and non-RGD-containing cell binding domains in fibrillin-1.
abstract: The fibrillins are large glycoprotein components of 10-nm microfibrils found in the extracellular matrix of most tissues. Microfibrils play a role in elastic fiber assembly and serve to link cells to elastic fibers in the extracellular matrix. To determine whether fibrillin-1 specifically interacts with receptors on cells from fibrillin-rich tissues, we evaluated whether two cell types that produce different types of fibrillin can adhere to purified fibrillin-1 in cell adhesion assays. Our results indicate that both cell types attach and spread on fibrillin-1 and that the RGD sequence in the fourth 8-cysteine motif mediates this interaction. Fibroblast attachment to fibrillin-1 was sensitive to inhibition by antibodies to the alphavbeta3 receptor and by peptides encoding the RGD sequence in fibrillin-1 and the second RGD sequence in fibrillin-2. In contrast, adhesion of auricular chondroblasts to fibrillin-1 was only partially inhibited by these reagents, suggesting that some cell types recognize a second, non-RGD binding site within the fibrillin molecule. These findings confirm and extend ultrastructural studies that suggest a direct interaction between microfibrils and the cell surface and provide a functional explanation for how this association occurs.
authors.affiliation: Department of Cell Biology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: H
authors.initials: H
authors.lastname: Sakamoto
authors.forename: T
authors.initials: T
authors.lastname: Broekelmann
authors.forename: D A
authors.initials: DA
authors.lastname: Cheresh
authors.forename: F
authors.initials: F
authors.lastname: Ramirez
authors.forename: J
authors.initials: J
authors.lastname: Rosenbloom
authors.forename: R P
authors.initials: RP
authors.lastname: Mecham
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001665:Binding Sites; D002356:Cartilage / Q000166:cytology / Q000502:physiology*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D002852:Chromatography, Ion Exchange; D003545:Cysteine; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000378:metabolism; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D016023:Integrins / Q000276:immunology / Q000502:physiology; D008840:Microfilament Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009842:Oligopeptides / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054392:Adipokines
chemical_list: D000906:Antibodies; D003545:Cysteine; D016326:Extracellular Matrix Proteins; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D007074:Immunoglobulin G; D016023:Integrins; D008840:Microfilament Proteins; D009842:Oligopeptides; D010455:Peptides; C000605722:FBN1 protein, human; D054392:Adipokines; C000605723:FBN2 protein, human; C047981:arginyl-glycyl-aspartic acid