Towards cellular receptors for prions

Publisher Website
Google Scholar
Abstract
Transmissible spongiform encephalopathies (TSE) are attributed to the conversion of the cellular prion protein (PrPc) into an abnormal isoform (PrPsc). This can be caused by the invasion of living organisms by infectious particles, or be inherited due to mutations on the PrPc gene. One of the most intriguing problems of prion biology is the inability to generate the infectious agent in vitro. This argues strongly that other cellular proteins besides those added in test tubes or found in cellular preparations are necessary for infection. Despite recent progress in the understanding of prion pathology, the subcellular compartments in which the interaction and conversion of PrPc into PrPsc take place are still controversial. PrPc interacts with various macromolecules at the cell membrane, in endocytic compartments and in the secretory pathway, all of which may play specific roles in the internalisation of PrPsc and conversion of PrPc. A specific interacting protein required for the propagation of prions was originally proposed as a prion receptor, and later referred to as a ligand, a cofactor, protein X, or a partner. However, current studies indicate that PrPc associates with multi‐molecular complexes, which mediate a variety of functions in distinct cellular compartments. It is proposed that a deeper understanding of the mechanics of such interactions, coupled to a better knowledge of the corresponding signalling pathways and ensuing cellular responses, will have a major impact on the prevention and treatment of TSE. Copyright © 2003 John Wiley & Sons, Ltd.