THE CELLULAR ISOFORM OF THE PRION PROTEIN, PRPC, IS ASSOCIATED WITH CAVEOLAE IN MOUSE NEUROBLASTOMA (N(2)A) CELLS

A major component of the infectious particle causing spongiform enceph alopathies or prion diseases is an aberrant isoform (PrPSc) of a glyco syl-phosphatidylinositol (GPI)-anchored cell surface protein, PrPC. Th e cellular processes involved in the formation of PrPSc are unclear bu t involve the internalization of PrPC prior to conversion. Here, we de monstrate that PrPC is associated with caveolin, a structural protein component of caveolae. We show that PrPC and caveolin share similar de tergent characteristics and copurify in linear sucrose gradients. PrPC was protected from proteinase K digestion in the caveolin fraction bu t solubilizing the caveolae prior to proteinase K digestion rendered P rPC susceptible to proteinase K digestion. Our results indicate a phys ical association between PrPC and caveolin in N(2)a cells. The implica tion of these results in relation to prion biogenesis is discussed. (C ) 1995 Academic Press, Inc.