Topic
Fibrillin-2
About: Fibrillin-2 is a research topic. Over the lifetime, 45 publications have been published within this topic receiving 7750 citations.
Papers
TL;DR: Investigation of the connective tissue matrices of skin, lung, kidney, vasculature, cartilage, tendon, muscle, cornea, and ciliary zonule demonstrated its widespread distribution, and immunolocalization suggested that fibrillin is arrayed periodically along the individual microfibril and that individualmicrofibrils may be aligned within bundles.
Abstract: A new connective tissue protein, which we call fibrillin, has been isolated from the medium of human fibroblast cell cultures. Electrophoresis of the disulfide bond-reduced protein gave a single band with an estimated molecular mass of 350,000 D. This 350-kD protein appeared to possess intrachain disulfide bonds. It could be stained with periodic acid-Schiff reagent, and after metabolic labeling, it contained [3H]glucosamine. It could not be labeled with [35S]sulfate. It was resistant to digestion by bacterial collagenase. Using mAbs specific for fibrillin, we demonstrated its widespread distribution in the connective tissue matrices of skin, lung, kidney, vasculature, cartilage, tendon, muscle, cornea, and ciliary zonule. Electron microscopic immunolocalization with colloidal gold conjugates specified its location to a class of extracellular structural elements described as microfibrils. These microfibrils possessed a characteristic appearance and averaged 10 nm in diameter. Microfibrils around the amorphous cores of the elastic fiber system as well as bundles of microfibrils without elastin cores were labeled equally well with antibody. Immunolocalization suggested that fibrillin is arrayed periodically along the individual microfibril and that individual microfibrils may be aligned within bundles. The periodicity of the epitope appeared to match the interstitial collagen band periodicity. In contrast, type VI collagen, which has been proposed as a possible microfibrillar component, was immunolocalized with a specific mAb to small diameter microfilaments that interweave among the large, banded collagen fibers; it was not associated with the system of microfibrils identified by the presence of fibrillin.
1,141 citations
TL;DR: Immunolocalization data were consistent with the hypothesis that LTBP-1 is a fibrillin-associated protein present in certain tissues but not in others, and a model depicting the relationship between LT BP-1 and fibrillins microfibrils is proposed.
569 citations
TL;DR: The extracellular microfibril, 10-14 nm in diameter, performs a number of functions, including serving as the scaffolding for deposition of tropoelastin to form elastic fibers, the most prominent of which are the two fibrillins.
Abstract: The extracellular microfibril, 10-14 nm in diameter, performs a number of functions, including serving as the scaffolding for deposition of tropoelastin to form elastic fibers. A variety of proteins compose the structure of microfibrils, the most prominent of which are the two fibrillins. Fibrillin-1 is encoded by FBN1 on human chromosome 15q21 and fibrillin-2 is encoded by FBN2 on 5q23. Each fibrillin monomer contains a large number of epidermal growth factor-like motifs, most capable of binding calcium ions, and a few motifs resembling the binding protein for transforming growth factor beta. In vitro polymerization of fibrillin monomers produces 'beads on a string' structures that look on electron microscopy much like microfibrils purified from the extracellular matrices of a variety of tissues. Mutations in FBN1 produce Marfan syndrome, a pleiotropic autosomal dominant connective tissue disorder with prominent manifestations in the skeleton, eye and cardiovascular system. A number of conditions related to Marfan syndrome are also due to FBN1 mutations. Contractural arachnodactyly is due to mutations in FBN2. In this paper we review the published mutations in these genes, preliminary results of genotype-phenotype correlations, and speculations regarding molecular pathogenesis.
503 citations
TL;DR: A model for the arrangement of fibrillin monomers in microfibrils that reconciles structural and antibody binding data is proposed, and a set of disease-causing mutations are described that provide the first clues to the specificity of cbEFG interactions.
454 citations
TL;DR: A gene-targetting experiment in mice indicates that fibrillin-1 microfibrils are predominantly engaged in tissue homeostasis rather than elastic matrix assembly, which suggests that aortic dilation is due primarily to the failure by themicrofibrillar array of the adventitia to sustain physiological haemodynamic stress, and that disruption of the elastic network of the media is a secondary event.
Abstract: Aortic aneurysm and dissection account for about 2% of all deaths in industrialized countries; they are also components of several genetic diseases, including Marfan syndrome (MFS). The vascular phenotype of MFS results from mutations in fibrillin-1 (FBN1), the major constituent of extracellular microfibrils. Microfibrils, either associated with or devoid of elastin, give rise to a variety of extracellular networks in elastic and non-elastic tissues. It is believed that microfibrils regulate elastic fibre formation by guiding tropo-elastin deposition during embryogenesis and early post-natal life. Hence, vascular disease in MFS is thought to result when FBN1 mutations preclude elastic fibre maturation by disrupting microfibrillar assembly. Here we report a gene-targetting experiment in mice that indicates that fibrillin-1 microfibrils are predominantly engaged in tissue homeostasis rather than elastic matrix assembly. This finding, in turn, suggests that aortic dilation is due primarily to the failure by the microfibrillar array of the adventitia to sustain physiological haemodynamic stress, and that disruption of the elastic network of the media is a secondary event.
396 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 2 |
| 2020 | 1 |
| 2013 | 1 |
| 2012 | 3 |
| 2011 | 1 |
| 2010 | 3 |