title: Microfibril structure masks fibrillin-2 in postnatal tissues.
abstract: Fibrillin microfibrils are polymeric structures present in connective tissues. The importance of fibrillin microfibrils to connective tissue function has been demonstrated by the multiple genetic disorders caused by mutations in fibrillins and in microfibril-associated molecules. However, knowledge of microfibril structure is limited, largely due to their insolubility. Most previous studies have focused on how fibrillin-1 is organized within microfibril polymers. In this study, an immunochemical approach was used to circumvent the insolubility of microfibrils to determine the role of fibrillin-2 in postnatal microfibril structure. Results obtained from studies of wild type and fibrillin-1 null tissues, using monoclonal and polyclonal antibodies with defined epitopes, demonstrated that N-terminal fibrillin-2 epitopes are masked in postnatal microfibrils and can be revealed by enzymatic digestion or by genetic ablation of Fbn1. From these studies, we conclude that fetal fibrillin polymers form an inner core within postnatal microfibrils and that microfibril structure evolves as growth and development proceed into the postnatal period. Furthermore, documentation of a novel cryptic site present in EGF4 in fibrillin-1 underscores the molecular complexity and tissue-specific differences in microfibril structure.
authors.affiliation: Shriners Hospital for Children, 3101 SW Sam Jackson Park Rd., Portland, OR 97239, USA.
authors.forename: Noe L
authors.initials: NL
authors.lastname: Charbonneau
authors.forename: C Diana
authors.initials: CD
authors.lastname: Jordan
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Keene
authors.forename: Sui
authors.initials: S
authors.lastname: Lee-Arteaga
authors.forename: Harry C
authors.initials: HC
authors.lastname: Dietz
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Rifkin
authors.forename: Francesco
authors.initials: F
authors.lastname: Ramirez
authors.forename: Lynn Y
authors.initials: LY
authors.lastname: Sakai
mesh_terms: D000595:Amino Acid Sequence; D000650:Amnion / Q000737:chemistry; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002642:Chick Embryo; D004475:Ectoderm / Q000196:embryology / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005121:Extremities / Q000196:embryology; D005260:Female; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020894:Microfibrils / Q000378:metabolism* / Q000648:ultrastructure; D008840:Microfilament Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000737:chemistry; D054392:Adipokines
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines; C000605723:FBN2 protein, human; C000605724:Fbn1 protein, mouse; C000605728:Fbn2 protein, mouse
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