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Papers In Press, published online ahead of print November 28, 2001
J. Biol. Chem, 10.1074/jbc.M110583200
Submitted on November 2, 2001
Revised on November 28, 2001
Accepted on November 27, 2001

Versican interacts with fibrillin-1 and links extracellular microfibrils to other connective tissue networks

Zenzo Isogai, Anders Aspberg, Douglas R. Keene, Robert N. Ono, Dieter P. Reinhardt, and Lynn Y. Sakai

Department of Biochemistry and Molecular Biology, Oregon Health Sciences University and Shriners Hospital for Children, Portland, OR 97201

Corresponding Author: lys{at}shcc.org

Fibrillin-containing microfibrils are polymeric structures which are difficult to extract from connective tissues. Proteolytic digestion of tissues has been utilized to release microfibrils for study. Few of the molecules which 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 in 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 an assay using cell culture media. In assays using microfibrils, versican lectin domain demonstrated preferential binding compared to other lecticans. Binding was calcium-dependent. The binding site for versican in microfibrils is most likely within a region of fibrillin-1 between cbEGF domains 11-21. Human mutations in this region can result in severe forms of Marfan syndrome (?neonatal? Marfan syndrome). The connection between versican and fibrillin microfibrils may be functionally significant, particularly in cardiovascular tissues.


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