BIOSYNTHESIS OF THE PRION PROTEINS IN SCRAPIE-INFECTED CELLS IN CULTURE

Prions are small proteinaceous particles that transmit scrapie and oth er fatal encephalopathies of humans and animals, and that appear to be devoid of nucleic acids. The only known - and perhaps the sole - comp onent of the scrapie prion is an abnormal host-encoded protein, the sc rapie prion protein PrPSc. The biosynthesis of this pathological prote in in the host cell, which is thus of paramount importance to prion re plication, is still poorly understood. We are studying the biosynthesi s and degradation of the scrapie prion protein PrPSc and of its normal isoform PrPC in scrapie-infected rodent cells in culture. PrPC is anc hored to the plasma membrane through a glycosylphosphatidylinositol (G PI) moiety. In scrapie-infected mouse neuroblastoma N(2)a cells, PrPSc is formed post-translationally, probably from plasma membrane PrPC,in an unknown subcellular compartment that is readily accessible from th e plasma membrane. Transport along the secretory pathway is necessary for PrPSc synthesis. In contrast to PrPC, PrPSc accumulates intracellu larly, primarily in secondary lysosomes. The subcellular compartment(s ) in which PrPSc is formed remain to be determined.