NR ATCS
AU Haigh,C.L.; Edwards,K.; Brown,D.R.
TI Copper binding is the governing determinant of prion protein turnover
QU Molecular and Cellular Neurosciences 2005 Oct; 30(2): 186-96
PT journal article
AB The cellular isoform of the prion protein (PrPc) is located at the cell membrane, anchored externally by a glycosylphosphatidylinositol (GPI) anchor. It is a copper (Cu) binding glycoprotein with a rapid basal turnover. Previous studies have shown that exposure of cells to Cu causes internalisation of PrPc in vitro. In this study, we show that physiological levels of Cu promote internalisation of PrPc. Interaction between PrPc and Cu was found to be the overriding factor in stimulating the internalisation response with other metals showing no effect. Deletion mutation studies have shown that two domains are essential for copper-induced internalisation to occur. These two domains are the octameric repeat region, encompassing amino acids 51-89, and the palindromic region, amino acids 112-119 with the sequence AGAAAAGA. The decrease in detectable levels of PrPc at the cell surface following Cu treatment was found to be the result of rapid internalisation rather than loss into the surrounding environment. These results have implications for both normal metabolism of PrPc and the possible mechanism of conversion of PrPc to PrPsc.
IN Wenn das über den Glycosylphosphatidylinositol-Anker auf der Zelloberfläche hängende normale Prionprotein Kupferionen bindet, dann wird es beschleunigt ins Zellinnere zurück transportiert. Dadurch nimmt die Konzentration des zellulären Prionproteins auf der Zelle ab, aber wahrscheinlich in der Zelle zu. Welchen Einfluß dies insgesamt auf die TSE-Empfänglichkeit hat, ist schwer zu sagen. Die Autoren machen dazu im Abstract keine Aussage, aber die Stichworte sprechen für Experimente mit einer ursprünglich aus einer "grünen Meerkatze" (Cercopithecus aethiops) stammenden Zelllinie, die nur noch Mausprionprotein exprimiert.
MH Amino Acid Sequence; Animals; Cell Line; Cercopithecus aethiops; Copper/pharmacology/*physiology; DNA Primers; Gene Expression Regulation; Kinetics; Mice; Mice, Knockout; Molecular Sequence Data; Mutagenesis, Site-Directed; Prions/drug effects/genetics/*metabolism; Research Support, Non-U.S. Gov't
AD Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK
SP englisch
PO USA