Structure and expression of fibrillin-2, a novel microfibrillar component preferentially located in elastic matrices

Abstract

Abstract. During the previous cloning of the fibrillin gene (FBN1), we isolated a partial eDNA coding for a fibrillin-like peptide and mapped the corresponding gene (FBN2) to human chromosome 5. (Lee, B., M. Godfrey, E. Vitale, H. Hori, M. G. Mattei, M. Sarfarazi, P. Tsipouras, E 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 extracellular component structurally related to fibrillin. Work presented in this report clarifies this important point. Determination of the entire primary structure of the FBN2 gene product demonstrated that this polypeptide is highly homologous to fibrillin. Immunoelectron microscopy localized both fibrillin proteins to elastin-associated extracellular mierofibrils. Finally, immunohistochemistry revealed that the fibrillins co-distribute in elastic and nonelastic connective tissues of the developing embryo, with preferential accumulation of the FBN2 gene product in elastic fiber-rich matrices. These results support the original hypothesis that the fibriUins may have distinct but related functions in the formation and maintenance of extracellular microfibrils. Accordingly, we propose to classify the FBN1 and FBN2 gene products as a new family of extracellular proteins and to name its members fibrillin-1 and fibrillin-2, respectively.

Xenopus fibrillin is expressed in the organizer and is the earliest component of matrix at the developing notochord‐somite boundary

“…This open reading frame lacked a start methionine, and is followed by a 3Ј untranslated region and poly-A tail. The protein derived from this open reading frame exhibited 68, 77, and 71% identity to the C-terminal portions of the human proteins fibrillin 1, 2, and 3, respectively, suggesting that XF is a homolog of fibrillin 2 (Maslen et al, 1991;Zhang et al, 1994;Corson et al, 2004) (Fig. 1).…”

“…Developmental expression of fibrillins has been described in post-gastrulation mouse, bird, and human embryogenesis (Zhang et al, 1994(Zhang et al, , 1995Quondamatteo et al, 2002;Visconti et al, 2003;Corson et al, 2004). These experiments reveal distinct patterns of embryonic expression for each of these fibrillin isoforms, but multiple fibrillins are generally expressed in a given tissue including developing heart and vasculature, notochord/axial structures, and developing lung, kidney, and limb bud.…”

New insights into elastic fiber assembly

“…While elastin arises from a single gene, the composition of microfibrils is more complex. The major structural element of microfibrils is contributed by the fibrillins (Sakai et al, 1986;Zhang et al, 1994). Numerous other proteins associate with microfibrils or with elastin itself, including the microfibril associated glycoproteins (MAGPs), fibulins and EMILIN-1 (for a complete list see Kielty et al, 2002).…”

Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma

“…Functional PCDH8 is frequently lost in breast cancer through both mutation and promoter methylation (Yu al., 2008), and also methylated in mantle cell lymphoma (Leshchenko et al, 2010). FBN2 and the related gene FBN1 encode large modular extracellular matrix glycoproteins, which are the key components of human microfibrils (Zhang et al, 1994). The microfibrillopathies, Marfan's syndrome and congenital contractural arachnodactyly, result from dominant mutations in FBN1 and FBN2, respectively (Robinson and Godfrey, 2000).…”