STRUCTURE AND EXPRESSION OF FIBRILLIN-2, A NOVEL MICROFIBRILLAR COMPONENT PREFERENTIALLY LOCATED IN ELASTIC MATRICES

During the previous cloning of the fibrillin gene (FBN1), we isolated a partial cDNA coding for a fibrillin-like peptide and mapped the corr esponding gene (FBN2) to human chromosome 5. (Lee, B., M. Godfrey, E. Vitale, H. Hori, M. G. Mattei, M. Sarfarazi, P. Tsipouras, F Ramirez, and D. W Hollister. 1991. Nature [Lond]. 352:330-334). The study left, however, unresolved whether or not the FBN2 gene product is an extrac ellular component structurally related to fibrillin. Work presented in this report clarifies this important point. Determination of the enti re primary structure of the FBN2 gene product demonstrated that this p olypeptide is highly homologous to fibrillin. Immunoelectron microscop y localized both fibrillin proteins to elastin-associated extracellula r microfibrils. Finally, immunohistochemistry revealed that the fibril lins co-distribute in elastic and nonelastic connective tissues of the developing embryo, with preferential accumulation of the FBN2 gene pr oduct in elastic fiber-rich matrices. These results support the origin al hypothesis that the fibrillins may have distinct but related functi ons in the formation and maintenance of extracellular microfibrils. Ac cordingly, we propose to classify the FBN1 and FBN2 gene products as a new family of extracellular proteins and to name its members fibrilli n-1 and fibrillin-2, respectively.