Inhibition of fibronectin matrix assembly by the heparin-binding domain ofvitronectin

The deposition of fibronectin into the extracellular matrix is an integrin- dependent, multistep process that is tightly regulated in order to ensure c ontrolled matrix deposition. Reduced fibronectin deposition has been associ ated with altered embryonic development, tumor cell invasion, and abnormal wound repair. In one of the initial steps of fibronectin matrix assembly, t he aminoterminal region of fibronectin binds to cell surface receptors, ter med matrix assembly sites. The present study was undertaken to investigate the role of extracellular signals in the regulation of fibronectin depositi on. Our data indicate that the interaction of cells with the extracellular glycoprotein, vitronectin, specifically inhibits matrix assembly site expre ssion and fibronectin deposition. The region of vitronectin responsible for the inhibition of fibronectin deposition was localized to the heparin-bind ing domain. Vitronectin's heparin-binding domain inhibited both beta(1) and non-beta(1) integrin-depend ent matrix assembly site expression and could be over come by treatment of cells with lysophosphatidic acid, an agent tha t promotes actin polymerization. The interaction of cells with the heparin- binding domain of vitronectin resulted in changes in actin microfilament or ganization and the subcellular distribution of the actin-associated protein s alpha-actinin and talin. These data suggest a mechanism whereby the hepar in-binding domain of vitronectin regulates the deposition of fibronectin in to the extracellular matrix through alterations in the organization of the actin cytoskeleton.