NR AVIL
AU Biswas,S.; Langeveld,J.P.M.; Tipper,D.; Lu,S.
TI Intracellular accumulation of a 46 kDa species of mouse prion protein as a result of loss of glycosylation in cultured mammalian cells
QU Biochemical and Biophysical Research Communications 2006 Oct 13; 349(1): 153-61
PT journal article
AB 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.
MH Animals; Brain/metabolism; Cells, Cultured; Cytoplasm/metabolism; Dimerization; Genetic Predisposition to Disease; Glycosylation; Golgi Apparatus/metabolism; Humans; Mice; Prion Diseases/metabolism; Prions/*biosynthesis/chemistry; Protein Structure, Tertiary; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
AD Laboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, 364 Plantation St., Worcester, MA 01605, USA
SP englisch
PO USA