NR AOQY
AU Campana,V.; Sarnataro,D.; Zurzolo,C.
TI PrPc association with lipid rafts in the early secretory pathway stabilizes its cellular conformation
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-122
PT Konferenz-Poster
AB The pathological conversion of PrPc into the PrPsc isoform appears to have a central role in the pathogenesis of Transmissible Spongiform Encephalopathies. However the identity of the intracellular compartment where this conversion occurs is still unknown. Several lines of evidence indicate that detergent-resistant lipid membrane domains (DRMs or rafts) could be involved in this process. We have characterized the association of PrPc to rafts during its biosynthesis. We found that PrPc associates with rafts already as an immature precursor in the Endoplasmic Reticulum. Interestingly, compared to the mature protein, the immature diglycosylated form has a different susceptibility to cholesterol depletion versus sphingolipid depletion, suggesting that the two forms associate with lipid domains of different composition. We also found that cholesterol depletion, which affects rafts association of the immature protein, slows down protein maturation and leads to protein misfolding. On the contrary, sphingolipid depletion, which affects the raft-association of the mature form, but not of the precursor, does not have any effect on the kinetics of protein maturation or on the conformation of the protein. These data indicate that the early association of PrPc with cholesterol-enriched rafts facilitates its correct folding and reinforce the hypothesis that cholesterol and sphingolipids have different roles in PrP metabolism.
AD V. Campana, D. Sarnataro, C. Zurzolo, Dipartimento di Biologia e Patologia Cellulare e Molecolare,Università degli Studi di Napoli Federico II, 80131 Napoli, Italy; C. Zurzolo, Department Biologie Cellulaire et Infections, Pasteur Institute, Paris, France
SP englisch
PO Deutschland