Cellular factors implicated in prion replication

Soto, Claudio; Morales, Rodrigo; Abid, Karim

Abstract

Prions are the unconventional infectious agents responsible for prion diseases, which are composed mainly by the misfolded prion protein (PrP(Sc)) that replicates by converting the host associated cellular prion protein (PrP(C)). Several lines of evidence suggest that other cellular components participate in prion conversion, however, the identity or even the chemical nature of such factors are entirely unknown. In this article we study the conversion factor activity by complementation of a PMCA procedure employing purified PrP(C) and PrP(Sc). Our results show that the conversion factor is present in all major organs of diverse mammalian species, and is predominantly located in the lipid raft fraction of the cytoplasmic membrane. On the other hand, it is not present in the lower organisms tested (yeast, bacteria and flies). Surprisingly, treatments that eliminate the major classes of chemical molecules do not affect conversion activity, suggesting that various different compounds may act as conversion factor in vitro. This conclusion is further supported by experiments showing that addition of various classes of molecules have a small, but detectable effect on enhancing prion replication in vitro. More research is needed to elucidate the identity of these factors, their detailed mechanism of action and whether or not they are essential component of the infectious particle. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

Más información

Título según WOS: ID WOS:000277793200040 Not found in local WOS DB
Título de la Revista: FEBS LETTERS
Volumen: 584
Número: 11
Editorial: Wiley
Fecha de publicación: 2010
Página de inicio: 2409
Página final: 2414
DOI:

10.1016/j.febslet.2010.04.040

Notas: ISI