The yeast Sup35NM domain propagates as a prion in mammalian cells

Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):462-7. doi: 10.1073/pnas.0811571106. Epub 2008 Dec 29.


Prions are infectious, self-propagating amyloid-like protein aggregates of mammals and fungi. We have studied aggregation propensities of a yeast prion domain in cell culture to gain insights into general mechanisms of prion replication in mammalian cells. Here, we report the artificial transmission of a yeast prion across a phylogenetic kingdom. HA epitope-tagged yeast Sup35p prion domain NM was stably expressed in murine neuroblastoma cells. Although cytosolically expressed NM-HA remained soluble, addition of fibrils of bacterially produced Sup35NM to the medium efficiently induced appearance of phenotypically and biochemically distinct NM-HA aggregates that were inherited by daughter cells. Importantly, NM-HA aggregates also were infectious to recipient mammalian cells expressing soluble NM-HA and, to a lesser extent, to yeast. The fact that the yeast Sup35NM domain can propagate as a prion in neuroblastoma cells strongly argues that cellular mechanisms support prion-like inheritance in the mammalian cytosol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Mice
  • Molecular Probe Techniques
  • Neuroblastoma / pathology*
  • Peptide Termination Factors
  • Prion Diseases / transmission*
  • Prions / adverse effects
  • Prions / biosynthesis*
  • Saccharomyces cerevisiae Proteins / adverse effects*
  • Tumor Cells, Cultured


  • Peptide Termination Factors
  • Prions
  • SUP35 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins