title: Sequestration of Sup35 by aggregates of huntingtin fragments causes toxicity of [PSI+] yeast.
abstract: Expression of huntingtin fragments with 103 glutamines (HttQ103) is toxic in yeast containing either the [PIN(+)] prion, which is the amyloid form of Rnq1, or [PSI(+)] prion, which is the amyloid form of Sup35. We find that HttQP103, which has a polyproline region at the C-terminal end of the polyQ repeat region, is significantly more toxic in [PSI(+)] yeast than in [PIN(+)], even though HttQP103 formed multiple aggregates in both [PSI(+)] and [PIN(+)] yeast. This toxicity was only observed in the strong [PSI(+)] variant, not the weak [PSI(+)] variant, which has more soluble Sup35 present than the strong variant. Furthermore, expression of the MC domains of Sup35, which retains the C-terminal domain of Sup35, but lacks the N-terminal prion domain, almost completely rescued HttQP103 toxicity, but was less effective in rescuing HttQ103 toxicity. Therefore, the toxicity of HttQP103 in yeast containing the [PSI(+)] prion is primarily due to sequestration of the essential protein, Sup35.
authors.affiliation: Laboratory of Cell Biology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-0301, USA.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhao
authors.forename: Yang-Nim
authors.initials: YN
authors.lastname: Park
authors.forename: Horia
authors.initials: H
authors.lastname: Todor
authors.forename: Christine
authors.initials: C
authors.lastname: Moomau
authors.forename: Daniel
authors.initials: D
authors.lastname: Masison
authors.forename: Evan
authors.initials: E
authors.lastname: Eisenberg
authors.forename: Lois E
authors.initials: LE
authors.lastname: Greene
mesh_terms: D015153:Blotting, Western; D005973:Glutamine / Q000235:genetics; D006801:Humans; D000071058:Huntingtin Protein; D018613:Microscopy, Confocal; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D010454:Peptide Termination Factors / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D011328:Prions / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014170:Transformation, Genetic; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D010454:Peptide Termination Factors; D011328:Prions; C404807:RNQ1 protein, S cerevisiae; C068068:SUP35 protein, S cerevisiae; C080775:SUP45 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D005973:Glutamine