Rdj2, a J protein family member, interacts with cellular prion PrP^C

PrP^C is a glycosylphosphatidylinositol (GPI) anchored glycoprotein of unknown function. Misfolding of normal cellular PrP^C to the pathogenic PrP^Sc is the hallmark of prion diseases (transmissible spongiform encephalopathies). Prion diseases are characterized by extensive neurodegeneration and early death. Understanding how PrP^C maintains its correct conformation is a major endeavor of current inquiry. Here we demonstrate a novel interaction between PrP^C and the J protein family member, Rdj2 (DjA2; Dj3, Dnj3, Cpr3, and Hirip4). The importance of the J protein family in the cellular folding machinery has been recognized for many years. The PrP^C/Rdj2 association was direct and concentration-dependent. Other J proteins such as CSPα and auxilin did not associate with PrP^C in the absence of ATP, demonstrating the specificity of the PrP^C/J protein interaction. These findings suggest that the J protein family serves as a 'folding catalyst' for PrP^C and implicates Rdj2 as a factor in the protection against prion diseases.