title: Fibrillin-1 microfibril deposition is dependent on fibronectin assembly.
abstract: Newly deposited microfibrils strongly colocalise with fibronectin in primary fibroblasts. Microfibril formation is grossly inhibited by fibronectin depletion, but rescued by supplementation with exogenous cellular fibronectin. As integrin receptors are key determinants of fibronectin assembly, we investigated whether they also influenced microfibril deposition. Analysis of beta1-integrin-receptor-null fibroblasts, blockage of cell surface integrin receptors that regulate fibronectin assembly and disruption of Rho kinase all result in suppressed deposition of both fibronectin and microfibrils. Antibody activation of beta1 integrins in fibronectin-depleted cultures is insufficient to rescue microfibril assembly. In fibronectin(RGE/RGE) mutant mouse fibroblast cultures, which do not engage alpha5beta1 integrin, extracellular assembly of both fibronectin and microfibrils is markedly reduced. Thus, pericellular microfibril assembly is regulated by fibronectin fibrillogenesis.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Science, Michael Smith Building, Oxford Road, University of Manchester, Manchester M139PT, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Kinsey
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Williamson
authors.forename: Shazia
authors.initials: S
authors.lastname: Chaudhry
authors.forename: Kieran T
authors.initials: KT
authors.lastname: Mellody
authors.forename: Amanda
authors.initials: A
authors.lastname: McGovern
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Takahashi
authors.forename: C Adrian
authors.initials: CA
authors.lastname: Shuttleworth
authors.forename: Cay M
authors.initials: CM
authors.lastname: Kielty
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000071838:Fibrillin-1; D000071837:Fibrillins; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D039081:Integrin alpha5beta1 / Q000037:antagonists & inhibitors / Q000502:physiology; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D020894:Microfibrils / Q000187:drug effects / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D008954:Models, Biological; D011108:Polymers / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D005353:Fibronectins; D039081:Integrin alpha5beta1; D019012:Integrin beta1; D008840:Microfilament Proteins; D011108:Polymers; D034741:RNA, Small Interfering; C000605722:FBN1 protein, human; D054392:Adipokines; C000605724:Fbn1 protein, mouse