title: Fibrillins can co-assemble in fibrils, but fibrillin fibril composition displays cell-specific differences.
abstract: Fibrillins are microfibril-forming extracellular matrix macromolecules that modulate skeletal development. In humans, mutations in fibrillins result in long bone overgrowth as well as other distinct phenotypes. Whether fibrillins form independent microfibrillar networks or can co-polymerize, forming a single microfibril, is not known. However, this knowledge is required to determine whether phenotypes arise because of loss of singular or composite functions of fibrillins. Immunolocalization experiments using tissues and de novo matrices elaborated by cultured cells demonstrated that both fibrillins can be present in the same individual microfibril in certain tissues and that both fibrillins can co-polymerize in fibroblast cultures. These studies suggest that the molecular information directing fibrillin fibril formation may be similar in both fibrillins. Furthermore, these studies provide a molecular basis for compensation of one fibrillin by the other during fetal life. In postnatal tissues, fibrillin-2 antibodies demonstrated exuberant staining in only one location: peripheral nerves. This surprising finding implicates distinct functions for fibrillin-2 in peripheral nerves, because a unique feature in humans and in mice mutant for fibrillin-2 is joint contractures that resolve over time.
authors.affiliation: Department of Biochemistry and Molecular Biology, Shriners Hospital for Children, Oregon Health and Science University, Portland 97201, USA.
authors.forename: Noe L
authors.initials: NL
authors.lastname: Charbonneau
authors.forename: Bette J
authors.initials: BJ
authors.lastname: Dzamba
authors.forename: Robert N
authors.initials: RN
authors.lastname: Ono
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Keene
authors.forename: Glen M
authors.initials: GM
authors.lastname: Corson
authors.forename: Dieter P
authors.initials: DP
authors.lastname: Reinhardt
authors.forename: Lynn Y
authors.initials: LY
authors.lastname: Sakai
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002460:Cell Line; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D000071840:Fibrillin-2; D000071837:Fibrillins; D005347:Fibroblasts / Q000378:metabolism; D005822:Genetic Vectors; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; C000605723:FBN2 protein, human; C000605728:Fbn2 protein, mouse; D000071840:Fibrillin-2; D000071837:Fibrillins; D008840:Microfilament Proteins; D011994:Recombinant Proteins