%0 Journal Article
%T Prion subcellular fractionation reveals infectivity spectrum, with a high titre-low PrPres level disparity
%A Victoria Lewis
%A Cathryn L Haigh
%A Colin L Masters
%A Andrew F Hill
%A Victoria A Lawson
%A Steven J Collins
%J Molecular Neurodegeneration
%D 2012
%I BioMed Central
%R 10.1186/1750-1326-7-18
%X Subcellular fractions enriched in lipid rafts or endoplasmic reticulum/mitochondrial marker proteins were equally highly efficient at prion transmission, despite lipid raft fractions containing up to eight times the levels of detectable PrPres. Brain homogenate infectivity was not differentially enhanced by subcellular fraction-specific co-factors, and proteinase K pre-treatment of selected fractions modestly, but equally reduced infectivity. Only lipid raft associated infectivity was enhanced by sonication.This study authenticates a subcellular disparity in PrPres and infectivity levels, and eliminates simultaneous divergence of prion strains as the explanation for this phenomenon. On balance, the results align best with the concept that transmission efficiency is influenced more by intrinsic characteristics of the infectious prion, rather than cellular microenvironment conditions or absolute PrPres levels.Prion diseases constitute a group of unique neurodegenerative disorders, which naturally afflict a number of mammalian species including humans. Although our understanding remains incomplete, considerable evidence supports the "protein-only" hypothesis, which purports that the agent ("prion") responsible for both transmission and consequent pathogenesis is predominantly composed of misfolded conformers of the normal cellular prion protein PrPC [1]. Additional discriminating features of the aberrant prion protein include increased ¦Â-sheet content [2,3], reduced solubility and increased tendency to aggregate, and typically heightened protease resistance [4-6]. Due to the characteristic protease resistant core, limited proteolysis with proteinase K (PK) truncates the N-terminus of the misfolded protein, producing PrPres, whilst PrPC is completely degraded, allowing a convenient biochemical differentiation of these two prion protein isoforms.An intriguing but somewhat perplexing aspect of prion biology is the several instances in transmission studies, encompassing ma
%K Prion protein
%K Prion infectivity
%K Prion disease
%K Protease resistance
%K Subcellular localisation
%K Fractionation
%U http://www.molecularneurodegeneration.com/content/7/1/18