Role of lipid rafts and GM1 in the segregation and processing of prion protein

PLoS One. 2014 May 23;9(5):e98344. doi: 10.1371/journal.pone.0098344. eCollection 2014.


The prion protein (PrPC) is highly expressed within the nervous system. Similar to other GPI-anchored proteins, PrPC is found in lipid rafts, membrane domains enriched in cholesterol and sphingolipids. PrPC raft association, together with raft lipid composition, appears essential for the conversion of PrPC into the scrapie isoform PrPSc, and the development of prion disease. Controversial findings were reported on the nature of PrPC-containing rafts, as well as on the distribution of PrPC between rafts and non-raft membranes. We investigated PrPC/ganglioside relationships and their influence on PrPC localization in a neuronal cellular model, cerebellar granule cells. Our findings argue that in these cells at least two PrPC conformations coexist: in lipid rafts PrPC is present in the native folding (α-helical), stabilized by chemico-physical condition, while it is mainly present in other membrane compartments in a PrPSc-like conformation. We verified, by means of antibody reactivity and circular dichroism spectroscopy, that changes in lipid raft-ganglioside content alters PrPC conformation and interaction with lipid bilayers, without modifying PrPC distribution or cleavage. Our data provide new insights into the cellular mechanism of prion conversion and suggest that GM1-prion protein interaction at the cell surface could play a significant role in the mechanism predisposing to pathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • G(M1) Ganglioside* / chemistry
  • G(M1) Ganglioside* / metabolism
  • Lipid Bilayers / chemistry
  • Lipid Bilayers / metabolism
  • Membrane Microdomains* / chemistry
  • Membrane Microdomains* / metabolism
  • Neurons / metabolism
  • PrPC Proteins* / chemistry
  • PrPC Proteins* / metabolism
  • PrPSc Proteins* / chemistry
  • PrPSc Proteins* / metabolism
  • Protein Structure, Secondary
  • Proteolysis*
  • Rats
  • Rats, Sprague-Dawley


  • Lipid Bilayers
  • PrPC Proteins
  • PrPSc Proteins
  • G(M1) Ganglioside

Grant support

This investigation was supported by grants from MIUR (Rome, Italy) Prin 2008 (prot. 200833SZ2F) and FAR 60% 2010-2011 to PP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.