title: The yeast Sup35NM domain propagates as a prion in mammalian cells.
abstract: 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.
authors.affiliation: Institute of Virology, Technische Universität München, Trogerstrasse 30, 81675 Munich, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Krammer
authors.forename: Dmitry
authors.initials: D
authors.lastname: Kryndushkin
authors.forename: Michael H
authors.initials: MH
authors.lastname: Suhre
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Andreas
authors.initials: A
authors.lastname: Hofmann
authors.forename: Alexander
authors.initials: A
authors.lastname: Pfeifer
authors.forename: Thomas
authors.initials: T
authors.lastname: Scheibel
authors.forename: Reed B
authors.initials: RB
authors.lastname: Wickner
authors.forename: Hermann M
authors.initials: HM
authors.lastname: Schätzl
authors.forename: Ina
authors.initials: I
authors.lastname: Vorberg
mesh_terms: 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
chemical_list: D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins