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| Versican interacts with fibrillin-1 and links extracellular microfibrils to other connective tissue networks |
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| Author(s): Isogai Z, Aspberg A, Keene DR, Ono RN, Reinhardt DP, Sakai LY |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 277 Issue: 6 Pages: 4565-4572 Published: FEB 8 2002 |
| Times Cited: 85 References: 50 |
| Abstract: Fibrillin-containing microfibrils are polymeric structures that are difficult to extract from connective tissues. Proteolytic digestion of tissues has been utilized to release microfibrils for study. Few of the molecules that connect microfibrils to other elements in the matrix have been identified. In this study, electron microscopic immunolocalization of anti-versican antibodies in tissues and in extracted microfibrils demonstrated that the C-terminal region of versican is found associated with fibrillin microfibrils. Extraction of microfibrils followed by treatment of microfibrils under dissociating conditions suggested that the versican C terminus is covalently bound to microfibrils. Binding assays using recombinant fibrillin-1 polypeptides and recombinant lectican lectin domains indicated that the versican lectin domain binds to specific fibrillin-1 polypeptides. The versican lectin domain also bound to molecules comigrating with authentic fibrillin-1 monomers in anassay using cell culture medium. In assays using microfibrils, the versican lectin domain demonstrated preferential binding compared with other lecticans. Binding was calcium-dependent. The binding site for versican in microfibrils is most likely within a region of fibrillin-1 between calcium-binding epidermal growth factor-like domains 11 and 21. Human mutations irk this region can result in severe forms of the Marfan syndrome ("neonatal" Marfan syndrome). The connection between versican and fibrillin microfibrils may be functionally significant, particularly in cardiovascular tissues. |
| Document Type: Article |
| Language: English |
| Reprint Address: Sakai, LY (reprint author), Shriners Hosp Children, 3101 SW Sam Jackson Pk Rd, Portland, OR 97201 USA |
Addresses:
1. Shriners Hosp Children, Portland, OR 97201 USA
2. Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA
3. Lund Univ, Sect Connect Tissue Biol, Dept Cell & Mol Biol, SE-22184 Lund, Sweden
4. Med Univ Lubeck, Dept Med Mol Biol, D-23538 Lubeck, Germany |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: 520ZP |
| ISSN: 0021-9258 |
| DOI: 10.1074/jbc.M110583200 |
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