An investigation into the subcellular localisation of co-factors that stimulate prion protien conversion: abstract

J.F. Graham, S. Agarwal, D. Kurian, L. Kirby, T.J.T. Pinheiro, A.C. Gill

Research output: Contribution to journalMeeting abstractpeer-review


Transmissible spongiform encephalopathies (TSEs) are a group
of fatal neurodegenerative disorders affecting humans and animals.
Different TSE strains are thought to be encoded by different
conformations of the prion protein and strain specific
co-factors may aid the conversion of the host protein (PrPC) to
a strain-specific misfolded form, PrPSc. We investigated the subcellular
localisation of molecules enhancing prion conversion in
TSE-susceptible cell lines and in scrapie associated fibrils (SAF)
from TSE-infected mouse brains, assaying for their presence by
use of a cell free conversion assay (CFCA) and an oligomerisation
assay. Plasma membrane enriched fractions from the LD9 cell
line enhanced the conversion efficiency of ME7 and 79A mouse
scrapie in the CFCA yet inhibited in vitro oligomerisation of
recombinant prion protein, suggesting the existence of separate,
competing mechanisms of specific and non-specific misfolding
in vivo. Mass spectrometric analysis of SAF from three different
strains of mouse scrapie showed different proteinaceous constituents
of fibrils. These initial experiments provide the basis for the
identification of the molecular make-up of different prion strains
through subsequent fractionations of plasma membrane derived
fractions or supplementation of these misfolding assays with
SAF-derived molecules.
Original languageUndefined/Unknown
Article number PPo1-11
Pages (from-to)122
Number of pages1
Issue number3
Publication statusPublished - Jul 2010
EventPrion 2010 - Salzburg, Austria
Duration: 8 Sep 201011 Sep 2010

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