MALARIA CIRCUMSPOROZOITE PROTEIN BINDS TO HEPARAN-SULFATE PROTEOGLYCANS ASSOCIATED WITH THE SURFACE-MEMBRANE OF HEPATOCYTES

During feeding by infected mosquitoes, malaria sporozoites are injecte d into the host's bloodstream and enter hepatocytes within minutes. Th e remarkable target cell specificity of this parasite may be explained by the presence of receptors for the region II-plus of the circumspor ozoite protein (CS) on the basolateral domain of the plasma membrane o f hepatocytes. We have now identified these receptors as heparan sulfa te proteoglycans (HSPG). The binding of CS to the receptors is abolish ed by heparitinase treatment, indicating that the recognition of regio n II-plus is via the glycosaminoglycan chains. We have purified and pa rtially characterized the CS-binding HSPGs from HepG2 cells. They have a molecular weight of 400,000-700,000, are tightly associated with th e plasma membrane, and are released from the cell surface by very mild trypsinization, a property which the CS receptors share with the synd ecan family of proteoglycans.