Fatal Familial Insomnia: Pathogenesis caused by a mutation affecting the metabolism of the normal prion protein. By Sabrina T. Gillig BIO-475 Seminar Dr. Peter Lin.
Fatal Familial Insomnia: Pathogenesis caused by a mutation affecting the metabolism of the normal prion protein.By Sabrina T. GilligBIO-475 SeminarDr. Peter Lin
Petersen, R.B., P. Parchi, S.L. Richardson, C.B. Urig, and P. Gambetti. 1996. Effect of the D178N mutation and the codon 129 polymorphism on the metabolism of the prion protein. The Journal of Biological Chemistry 271: 12661-12668.
By using the antibiotic tunicamycin (which prevents glycosylation in newly synthesized proteins), effect of the glycosylation in the transport of the PrPm was evaluated.
is degraded inside the cell, while the normal PrPc necessitates glycosylation to reach the cell surface.
In order to find out whether PrPm is degraded when kept in the ER-Golgi compartment scientists used brefeldin A (which blocks transport of glycosylated proteins from the ER to the Golgi complex).
All three glycoforms were observed
Mutant cells exhibited degradation or change to the glycosylated form
→More unglycosylated PrPm reaches the cell surface when valine is present in codon 129.