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J Biol Chem, Vol. 274, Issue 38, 27257-27264, September 17, 1999
Inhibition of Fibronectin Matrix Assembly by the Heparin-binding
Domain of Vitronectin
Denise C.
Hocking,
Jane
Sottile,
Thomas
Reho,
Reinhard
Fässler§, and
Paula J.
McKeown-Longo
From the Cell and Molecular Biology Program and the Department of
Physiology and Cell Biology, Albany Medical College, Albany, New York
12208 and the § Department of Experimental Pathology, Lund
University, 22185 Lund, Sweden
The deposition of fibronectin into the
extracellular matrix is an integrin-dependent, multistep
process that is tightly regulated in order to ensure controlled matrix
deposition. Reduced fibronectin deposition has been associated with
altered embryonic development, tumor cell invasion, and abnormal wound
repair. In one of the initial steps of fibronectin matrix assembly, the
amino-terminal region of fibronectin binds to cell surface receptors,
termed matrix assembly sites. The present study was undertaken to
investigate the role of extracellular signals in the regulation of
fibronectin deposition. Our data indicate that the interaction of cells
with the extracellular glycoprotein, vitronectin, specifically inhibits matrix assembly site expression and fibronectin deposition. The region
of vitronectin responsible for the inhibition of fibronectin deposition
was localized to the heparin-binding domain. Vitronectin's heparin-binding domain inhibited both 1 and
non- 1 integrin-dependent matrix assembly
site expression and could be overcome by treatment of cells with
lysophosphatidic acid, an agent that promotes actin polymerization. The
interaction of cells with the heparin-binding domain of vitronectin
resulted in changes in actin microfilament organization and the
subcellular distribution of the actin-associated proteins -actinin
and talin. These data suggest a mechanism whereby the heparin-binding
domain of vitronectin regulates the deposition of fibronectin into the
extracellular matrix through alterations in the organization of the
actin cytoskeleton.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
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