title: The fibrillin microfibril scaffold: A niche for growth factors and mechanosensation?
abstract: The fibrillins, large extracellular matrix molecules, are polymerized to form "microfibrils." The fibrillin microfibril scaffold is populated by microfibril-associated proteins and by growth factors, which are likely to be latent. The scaffold, associated proteins, and bound growth factors, together with cellular receptors that can sense the microfibril matrix, constitute the fibrillin microenvironment. Activation of TGFβ signaling is associated with the Marfan syndrome, which is caused by mutations in fibrillin-1. Today we know that mutations in fibrillin-1 cause the Marfan syndrome as well as Weill-Marchesani syndrome (and other acromelic dysplasias) and result in opposite clinical phenotypes: tall or short stature; arachnodactyly or brachydactyly; joint hypermobility or stiff joints; hypomuscularity or hypermuscularity. We also know that these different syndromes are associated with different structural abnormalities in the fibrillin microfibril scaffold and perhaps with specific cellular receptors (mechanosensors). How does the microenvironment, framed by the microfibril scaffold and populated by latent growth factors, work? We must await future investigations for the molecular and cellular mechanisms that will answer this question. However, today we can appreciate the importance of the fibrillin microfibril niche as a contextual environment for growth factor signaling and potentially for mechanosensation.
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Sengle
authors.affiliation: Shriners Hospital for Children, Oregon Health & Science University, Portland, OR, United States. Electronic address: lys@shcc.org.
authors.forename: Lynn Y
authors.initials: LY
authors.lastname: Sakai
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D008382:Marfan Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D040542:Mechanotransduction, Cellular; D020894:Microfibrils / Q000502:physiology*; D008840:Microfilament Proteins / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D054392:Adipokines
chemical_list: D019485:Bone Morphogenetic Proteins; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D016212:Transforming Growth Factor beta; C000605722:FBN1 protein, human; D054392:Adipokines
keywords: Bone morphogenetic protein; Fibrillin; LTBP; Marfan syndrome; Mechanosensation; TGFβ; Weill–Marchesani syndrome