The fibrillin-marfan syndrome connection

✍ Scribed by Francesco Ramirez; Lygia Pereira; Hui Zhang; Brendan Lee

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 743 KB
• Volume: 15
• Category: Article
• ISSN: 0265-9247
• DOI: 10.1002/bies.950150904

✦ Synopsis

A few years ago no one would have suspected that the well-known disorder of connective tissue, Marfan syndrome, could be caused by mutations in a recently discovered extracellular component, fibrillin. Likewisc, nobody would have predicted that fibrillin represents a small family of proteins that are associated with several phenotypically overlapping disorders. The fibrillins arc integral constituents of the non-collagenous microfibrils, with an average diameter of 10 nm. These aggregates are distributed in the extracellular matrix of virtually every tissue. Microfihrillar bundles provide the external coating to elastin in elastic fibers, and serve an anchoring function in non-elastic tissues. At higher resolution, individual microfibrils have a "beads-on-a-string" appearance resulting from the head-to-tail polymerization of multiple fibrillin aggregates. Structurally, fibrillin contains a series of repeated sequences homologous to the epidermal growth factor calcium-binding motif. Characterization of fibrillin mutations in Marfan syndrome patients, together with the elucidation of the structure of the fibrillin proteins, have provided new insights, and raised new questions, about the function of the 10 nm microfibrils. For example, it is possible that the fibrillins, in addition to serving a structural function, might also be involved in regulating cellular activities and morphogenetic programs. It is fitting that the long search for the Marfan syndrome gene has brought a novel group of proteins to the forefront of extracellular matrix biology.