Intracellular accumulation of a 46 kDa species of mouse prion protein as a result of loss of glycosylation in cultured mammalian cells

UMMS Affiliation

Laboratory of Nucleic Acid Vaccines, Department of Medicine; Department of Molecular Genetics and Microbiology; Department of Microbiology and Physiological Systems

Publication Date


Document Type



Biochemistry, Biophysics, and Structural Biology | Microbiology | Physiology


Prion diseases are fatal neurodegenerative disorders characterized by the accumulation of an abnormal isoform (PrPSc) of the normal cellular prion protein (PrPC) in the brain. Reportedly, abnormal N-linked glycosylation patterns in PrPC are associated with disease susceptibility; thus, we compared the glycosylation status of normal and several mutant forms of the murine prion protein (MuPrP) in cultured mammalian cells. Substitution of the N-terminal signal sequence of normal MuPrP with a heterologous signal peptide did not alter glycosylation. When expressed without the C-terminal glycophosphatidylinositol anchor signal, the majority of MuPrP remained intracellular and unglycosylated, and a 46 kDa species (p46) of the unglycosylated PrPC was detected on reducing gels. p46 was also observed when wild-type MuPrP was expressed in the presence of tunicamycin or enzymatically deglycosylated in vitro. A rabbit polyclonal anti-serum raised against dimeric MuPrP cross-reacted with p46 and localized the signal within the Golgi apparatus. We propose that the 46 kDa signal is a dimeric form of MuPrP and in the light of recent studies, it can be argued that a relatively stable, non-glycosylated, cytoplasmic PrPC dimer, produced as a result of compromised glycosylation is an intermediate in initiating conversion of PrPC to PrPSc in sporadic transmissible spongiform encephalopathies.

DOI of Published Version



Biochem Biophys Res Commun. 2006 Oct 13;349(1):153-61. Epub 2006 Aug 14. Link to article on publisher's site

Journal/Book/Conference Title

Biochemical and biophysical research communications

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PubMed ID