NR AOMM
AU Peters,P.J.; Mironov,A.Jr.; Peretz,D.; van Donselaar,E.; Leclerc,E.; Erpel,S.; DeArmond,S.J.; Burton,D.R.; Williamson,R.A.; Vey,M.; Prusiner,S.B.
TI Trafficking of prion proteins through a caveolae-mediated endosomal pathway
QU Journal of Cell Biology 2003 Aug 18; 162(4): 703-17
PT journal article
AB To understand the posttranslational conversion of the cellular prion protein (PrPc) to its pathologic conformation, it is important to define the intracellular trafficking pathway of PrPc within the endomembrane system. We studied the localization and internalization of PrPc in CHO cells using cryoimmunogold electron microscopy. At steady state, PrPc was enriched in caveolae both at the TGN and plasma membrane and in interconnecting chains of endocytic caveolae. Protein A-gold particles bound specifically to PrPc on live cells. These complexes were delivered via caveolae to the pericentriolar region and via nonclassical, caveolae-containing early endocytic structures to late endosomes/lysosomes, thereby bypassing the internalization pathway mediated by clathrin-coated vesicles. Endocytosed PrPc-containing caveolae were not directed to the ER and Golgi complex. Uptake of caveolae and degradation of PrPc was slow and sensitive to filipin. This caveolae-dependent endocytic pathway was not observed for several other glycosylphosphatidyl inositol (GPI)-anchored proteins. We propose that this nonclassical endocytic pathway is likely to determine the subcellular location of PrPc conversion.
MH Animal; Bacterial Proteins/metabolism; CHO Cells; Caveolae/*metabolism/ultrastructure; Caveolins/biosynthesis/genetics; Endosomes/metabolism/ultrastructure; Gold Colloid/metabolism; Hamsters; Microscopy, Electron; Prions/*metabolism; Protein Transport/physiology; Receptors, Transferrin/metabolism; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121-H4, 1066 CX Amsterdam, The Netherlands. p.peters@nki.nl
SP englisch
PO USA