Cellular Heparan Sulfate Participates in the Metabolism of Prions
Journal of Biological Chemistry
During prion diseases, the host protein PrP C is refolded into an abnormal conformer "prion" PrP Sc . Histological and pharmacological data have suggested that glycosaminoglycans may be involved in the development of prion diseases. Here we present the first direct evidence that cellular glycosaminoglycans play a role in the biogenesis of PrP Sc in prion-infected ScN2a cells. When ScN2a cells were incubated with estradiol ␤-Dxyloside to inhibit the glycosylation of proteoglycans, PrP Sc was
... ans, PrP Sc was vastly reduced. Treating ScN2a-M cells with heparinase III, but not with heparinase I or chondroitinase ABC, caused a profound reduction of PrP Sc . In contrast, neither the amount of PrP C nor its subcellular distribution were affected as assayed by immunofluorescence microscopy and flotation procedures. In vitro treatment of ScN2a membranes with heparinase III at either neutral or acidic pH did not reduce the level of protease-resistant PrP Sc . The inhibitor of sulfation, sodium chlorate, vastly reduces PrP Sc in ScN2a cells (Gabizon, R., Meiner, Z., Halimi, M., and Ben-Sasson, S. A. (1993) J. Cell. Physiol. 157, 319 -325). Both soluble heparan sulfate and chondroitin sulfate partially restored the level of PrP Sc in chlorate-treated cells. We conclude that heparinase III-sensitive, presumably undersulfated, cellular heparan sulfate plays a significant role in the biogenesis of PrP Sc in ScN2a cells.