NR APAE
AU Walshe,K.; Guinan,E.; Rogers,M.
TI Investigations into the role of caveolae and caveolin-1 in prion protein biology
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-54
PT Konferenz-Poster
AB
The prion diseases are a group of fatal neurodegenerative disorders, which are characterised by the presence of an aberrant isoform of a normal cellular protein, PrPc. The central event in these diseases has been postulated to be the conversion of PrPc to the pathogenic form, PrPsc. Identifying the subcellular location of, and the factors involved in, this conversion event is crucial in understanding these diseases. While it has been proposed that conversion occurs after maturation and transport of PrPc to the cell surface, there has been some controversy regarding it's exact cellular context. We have definitively demonstrated that PrPc is associated with membrane structures called caveolae.
Cavolae are membrane microdomains rich in cholesterol and many GPI anchored proteins that are suggested to be involved in endocytosis, potocytosis, cell signalling and Ca2+ signalling.
Both PrPc and PrPsc were found to be located in Caveolae using non-detergent gradient fractionation and furthermore an interaction was demonstrated between Caveolin-1 and PrPc by co-immunoprecipitation from ScN2a cells. Caveolin-1 is the major structural component of caveolae, the level of which is low but detectable in ScN2a cells. In order to investigate whether the conversion of PrPc to PrPsc is dependent on caveolae, caveolin-1 expression and thus caveolae formation was increased in ScN2a cells. Despite increasing caveolin-1 expression up to 30 fold no effect on either PrPsc levels or on the actual rate of PrPsc formation. Currently we are working to more clearly define the interaction between caveolin-1 and PrPc.
AD K. Walshe, E. Guinan, M. Rogers, Department of Zoology and Conway Institute of Biomolecular and Biomedical Sciences, U.C.D., Ireland
SP englisch
PO Deutschland