NON-GLYCOSAMINOGLYCAN BEARING DOMAINS OF PERLECAN AND AGGRECAN INFLUENCE THE UTILIZATION OF SITES FOR HEPARAN AND CHONDROITIN SULFATE SYNTHESIS

Perlecan and aggrecan are proteoglycans that receive primarily heparan sulfate and chondroitin sulfate side chains, respectively. Their larg e multidomained core proteins have little or no homology to each other and their glycosaminoglycan (GAG) attachment sites are restricted to certain domains only. We examined the involvement of the non-GAG beari ng domains in designating the GAG type added to the GAG attachment dom ain by preparing cDNA constructs that expressed perlecan/aggrecan chim eras as recombinant products in COS-7 cells and then determining the s ize and GAG composition of the recombinant products. The results showe d that domain I of perlecan receives primarily (73-81%) heparan sulfat e when coupled with domain II and III of perlecan, but when coupled wi th the G3 domain of aggrecan, it receives primarily (59-63%) chondroit in sulfate. Furthermore, the chondroitin sulfate attachment region of aggrecan received GAG side chains more readily when coupled to the G3 domain of aggrecan than when coupled to domains II and III of perlecan . The GAG side chains on all these recombinant products were small and similar in size. These findings indicate that the utilization of atta chment sites for heparan and chondroitin sulfate or the sulfation of t hese GAGs can be influenced, in part, by non-GAG bearing domains.