Key Points
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The fibulin protein family consists of five isoforms (fibulin-1, -2, -3, -4 and -5), which are localized to the extracellular matrix.
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Fibulin isoforms vary in size (50–200 kDa) and have an elongated multidomain structure that is dominated by numerous calcium-binding epidermal growth factor-like modules.
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The fibulins show a widespread deposition in various extracellular structures such as microfibrils, basement membranes and elastic fibres.
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The widespread distribution of fibulins correlates well with their broad binding repertoire for fibronectin, collagens, basement-membrane proteins, elastin and proteoglycans.
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The cell-biological activities of fibulins include the binding of integrin receptors and the modulation of cell proliferation and malignant transformation.
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New information on the biological roles of the fibulins is now becoming available from the analysis of inherited human diseases and transgenic animals.
Abstract
Fibulins are a newly recognized family of extracellular matrix proteins. The five known members of the family share an elongated structure and many calcium-binding sites, owing to the presence of tandem arrays of epidermal growth factor-like domains. They have overlapping binding sites for several basement-membrane proteins, tropoelastin, fibrillin, fibronectin and proteoglycans, and they participate in diverse supramolecular structures. New insights into their biological roles are now emerging from studies of transgenic mice and of some inherited human diseases.
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Acknowledgements
Part of the work described here was supported by research grants from the Deutsche Forschungsgemeinschaft for T.S. and R.T., the European Community for R.T., and the National Institutes of Health for M.-L.C. The authors are grateful to S. Argraves for communicating unpublished work and to J. Uitto for critically reading the manuscript.
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Glossary
- EDTA
-
(ethylenediamine tetra-acetic acid). A strong chelator of bivalent cations.
- Kd VALUE
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The equilibrium dissociation constant of bimolecular reactions.
- PERINEURAL TISSUE
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The tissue around a nerve or group of nerves.
- ELASTOTIC SKIN
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Skin that shows degenerative changes of the elastic fibres. The condition can be associated with skin diseases, ageing or prolonged exposure to sunlight.
- CONTACT DERMATITIS
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Itching, redness or inflammation of the skin that is caused by direct exposure to irritating substances, such as chemicals, metals, clothing, cosmetics and plants.
- ELASTINOPATHY
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Pathological changes of the elastic fibres that lead to various degenerative diseases.
- MESENCHYMAL TISSUE
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The tissue that originates from mesenchymal cells, which are unspecified cells that are derived mainly from the primitive mesoderm during embryogenesis. The connective tissues of the body develop from the mesenchymal cells.
- ANGIOGENESIS
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A process of blood-vessel branching, in which blood vessels sprout from small capillaries.
- RGD-DEPENDENT INTEGRINS
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A specific group of cellular integrin receptors that bind to the arginine-glycine-aspartate (RGD) sequences of their ligands.
- WERNER SYNDROME
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A premature ageing disorder that is inherited in an autosomal recessive mode. The clinical symptoms can include short stature, wrinkled skin, baldness, cataracts and muscular atrophy.
- SYNPOLYDACTYLY
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A developmental defect that is characterized by the fusion (syndactyly) and splitting (polydactyly) of fingers or toes. It is usually an autosomal dominant disease and can result from mutations in the homeobox genes.
- MACULAR DEGENERATIVE DISEASE
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An incurable eye disease that is caused by the deterioration of the central portion of the retina, which is known as the macula. The disease is heterogeneous and includes the rare heritable forms, the sporadic early-onset form and the age-related form.
- MARFAN SYNDROME
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A heritable connective tissue disease that affects several organ systems, including the skeleton, eyes, lungs, heart and blood vessels. The disease is caused by dominant mutations in the fibrillin-1 gene.
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Timpl, R., Sasaki, T., Kostka, G. et al. Fibulins: a versatile family of extracellular matrix proteins. Nat Rev Mol Cell Biol 4, 479–489 (2003). https://doi.org/10.1038/nrm1130
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