INTERACTIONS BETWEEN FIBRONECTIN AND CHONDROITIN SULFATE ARE MODULATED BY MOLECULAR CONTEXT

Interactions between fibronectin (FN) and glycosaminoglycans are essen tial for extracellular matrix morphology and cell adhesion. One of the most abundant glycosaminoglycans is chondroitin sulfate, and here we show that recombinant FNs (deminectins (DN)) containing the carboxyl-t erminal cell, heparin, and fibrin domains bind specifically to chondro itin sulfate in affinity chromatography assays. Using a panel of mutan t DNs, important determinants for chondroitin sulfate binding have bee n localized to repeats III13 and III14 within the heparin domain. In p articular, mutation of an arginine pair in repeat III13 to neutral res idues ablated binding to chondroitin sulfate as we previously reported for heparin (Barkalow, F.J.B., and Schwarzbauer, J.E. (1991) J. Biol. Chen. 266, 7812-7818). These results, in combination with the ability of heparin and chondroitin sulfate to compete for binding to DNs, dem onstrate that these two glycosaminoglycans interact with similar or ov erlapping sites in FN. One important difference between FN interaction s with heparin and chondroitin sulfate is that, while FN and DNs bound equally to heparin, FN bound less efficiently than DNs to chondroitin sulfate. Reduced binding to chondroitin sulfate was also observed wit h a larger recombinant FN lacking internal repeats III1-7 indicating t hat the amino-terminal region acts to limit binding to the carboxyl-te rminal domain. Our results demonstrate that interactions between FN an d chondroitin sulfate are modulated by molecular context.