The role of pre-existing aggregates in Hsp104-dependent polyglutamine aggregate formation and epigenetic change of yeast prions.
Amyloid-like protein aggregates have been implicated in various diseases and in the protein-based inheritance of yeast prions. The molecular chaperone Hsp104 has been shown to be necessary for the aggregate formation of polyglutamine in yeast, and for the maintenance of several yeast prion phenotypes through the formation of self-propagating aggregates. In this paper, we show that the polyglutamine aggregates that are formed independently of Hsp104, are required for Hsp104 to efficiently produce more aggregates. Similarly, in the yeast prion [PSI+] system, Hsp104-dependent epigenetic changes to the [PSI+] prion phenotype require the presence of prion aggregates in the normal [psi-] state. We also show that the co-localization of different prion aggregates suggests that cross-seeding by different yeast prions increases the probability of Hsp104-dependent epigenetic change. These findings highlight the role of pre-existing aggregates in chaperone-dependent establishment of the epigenetic trait in yeast prions, and possibly in the pathology of several neurodegenerative diseases.
Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, 3-18-22, Honkomagome, Bunkyo, 113-8613, Japan. ykimura@rinshoken.or.jp
Yoko
Y
Kimura
Sumiko
S
Koitabashi
Akira
A
Kakizuka
Takashi
T
Fujita
D044127:Epigenesis, Genetic; D017353:Gene Deletion; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D010454:Peptide Termination Factors; D010455:Peptides / Q000737:chemistry*; D010957:Plasmids; D011328:Prions / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
D006360:Heat-Shock Proteins; D010454:Peptide Termination Factors; D010455:Peptides; D011328:Prions; C404807:RNQ1 protein, S cerevisiae; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae; C097188:polyglutamine