The yeast Sup35NM domain propagates as a prion in mammalian cells.
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.
Krammer
Carmen
C
Institute of Virology, Technische Universität München, Trogerstrasse 30, 81675 Munich, Germany.
Kryndushkin
Dmitry
D
Suhre
Michael H
MH
Kremmer
Elisabeth
E
Hofmann
Andreas
A
Pfeifer
Alexander
A
Scheibel
Thomas
T
Wickner
Reed B
RB
Schätzl
Hermann M
HM
Vorberg
Ina
I
D000818:Animals; D051379:Mice; D015336:Molecular Probe Techniques; D009447:Neuroblastoma / Q000473:pathology*; D010454:Peptide Termination Factors; D017096:Prion Diseases / Q000635:transmission*; D011328:Prions / Q000009:adverse effects / Q000096:biosynthesis*; D029701:Saccharomyces cerevisiae Proteins / Q000009:adverse effects*; D014407:Tumor Cells, Cultured
D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins