title: Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo.
abstract: Extracellular elastic fibres provide mechanical elasticity to tissues and contribute towards the processes of organ remodelling by affecting cell-cell signalling. The formation of elastic fibres requires the assembly and crosslinking of tropoelastin monomers, and organization of the resulting insoluble elastin matrix into functional fibres. The molecules and mechanisms involved in this process are unknown. Fibulin-5 (also known as EVEC/DANCE) is an extracellular matrix protein abundantly expressed in great vessels and cardiac valves during embryogenesis, and in many adult tissues including the aorta, lung, uterus and skin, all of which contain abundant elastic fibres. Here we show that fibulin-5 is a calcium-dependent, elastin-binding protein that localizes to the surface of elastic fibres in vivo. fibulin-5-/- mice develop marked elastinopathy owing to the disorganization of elastic fibres, with resulting loose skin, vascular abnormalities and emphysematous lung. This phenotype, which resembles the cutis laxa syndrome in humans, reveals a critical function for fibulin-5 as a scaffold protein that organizes and links elastic fibres to cells. This function may be mediated by the RGD motif in fibulin-5, which binds to cell surface integrins, and the Ca2+-binding epidermal growth factor (EGF) repeats, which bind elastin.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, Texas 75390, USA. hyanagisawa@aol.com
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yanagisawa
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Davis
authors.forename: Barry C
authors.initials: BC
authors.lastname: Starcher
authors.forename: Takashi
authors.initials: T
authors.lastname: Ouchi
authors.forename: Masashi
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: James A
authors.initials: JA
authors.lastname: Richardson
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000196:embryology / Q000473:pathology; D004547:Elastic Tissue / Q000196:embryology / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D004549:Elastin / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018390:Gene Targeting; D008168:Lung / Q000196:embryology / Q000473:pathology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D016326:Extracellular Matrix Proteins; C120769:Fbln5 protein, mouse; D009842:Oligopeptides; D011994:Recombinant Proteins; C047981:arginyl-glycyl-aspartic acid; D004549:Elastin