CELL-ADHESION TO A MOTIF SHARED BY THE MALARIA CIRCUMSPOROZOITE PROTEIN AND THROMBOSPONDIN IS MEDIATED BY ITS GLYCOSAMINOGLYCAN-BINDING REGION AND NOT BY CSVTCG

The malaria circumsporozoite protein (CS), thrombospondin (TSP) and se veral other proteins including the terminal complement proteins and th e neural adhesion molecules F-spondin and Unc-5, share a cell adhesive sequence, In CS this sequence is designated as region II-plus (EWSPCS VTCGNGIQVRIK) and in TSP it is found in the type I repeats. Previous s tudies aimed at fine mapping the amino acid residues required for cell adhesion have yielded discrepant results. Here we show in three diffe rent cell lines that the downstream basic residues are required for ce ll adhesion whereas the CS-VTCG sequence is not, Using mutant Chinese hamster ovary cells selected for deficiencies in proteoglycan synthesi s, we show that in wild type cells, heparan sulfate proteoglycans are the binding sites for this motif, This finding is supported by additio nal experiments with two other cell lines demonstrating that treatment with heparitinase but not chondroitinase abolishes cell adhesion to p eptides representing this motif, Using Chinese hamster ovary cell muta nts deficient in heparan sulfate proteoglycans but possessing chondroi tin sulfate proteoglycans, we show that cell surface chondroitin sulfa te proteoglycans can also mediate binding to this motif although highe r concentrations of peptides are required for adhesion, Chondroitinase , but not heparitinase, treatment of these cells destroys cell surface -binding sites. Taken together, these results indicate that cell adhes ion to this motif involves an interaction between the downstream posit ively-charged residues and the negatively charged glycosaminoglycan ch ains of heparan sulfate, or in some cases chondroitin sulfate, proteog lycans on the cell surface.