Prion protein aggregation reverted by low temperature in transfected cells carrying a prion protein gene mutation

Academic Article

Abstract

  • Prion diseases are characterized by the conversion of the normal cellular prion protein (PrP(C)), a glycoprotein that is anchored to the cell membrane by a glycosylphosphatidylinositol moiety, into an isoform that is protease-resistant (PrP(res)) and pathogenic. In inherited prion diseases, mutations in the priori protein (PrP(M)) engender the conversion of PrP(M) into PrP(res). We developed a cell model of Gerstmann-Straussler-Scheinker disease, a neurodegenerative condition characterized by PrP(M)-containing amyloid deposits and neuronal loss, by expressing the Gerstmann-Straussler- Scheinker haplotype Q217R-129V in human neuroblastoma cells. By comparison to PrP(C), this genotype results in the following alterations of PrPM: 1) expression of an aberrant form lacking the glycosylphosphatidylinositol anchor, 2) increased aggregation and protease resistance, and 3) impaired transport to the cell surface. Most of these alterations are temperature- sensitive, indicating that they are due to misfolding of PrP(M).
  • Authors

    Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 27020647
  • Author List

  • Singh N; Zanusso G; Chen SG; Fujioka H; Richardson S; Gambetti P; Petersen RB
  • Start Page

  • 28461
  • End Page

  • 28470
  • Volume

  • 272
  • Issue

  • 45