The [<i>URE3</i>] phenotype: evidence for a soluble prion in yeast

Fernandez-Bellot, Eric; Guillemet, Elisabeth; Ness, Frédérique; Baudin-Baillieu, Agnès; Ripaud, Leslie; Tuite, Mick F.; Cullin, Christophe

doi:10.1093/embo-reports/kvf011

Cited by 25 publications

(26 citation statements)

References 21 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…the number or size of the aggregates. Also, in some cases no foci were detected in the cells containing GFP fusions to prions based on Sup35 and Ure2 (42,43). This phenotype is compatible with prions being polymers but with a low degree of aggregation.…”

Section: Polymers and Aggregates: Two Levels In The Structure Ofmentioning

confidence: 77%

Yeast [PSI+] Prion Aggregates Are Formed by Small Sup35 Polymers Fragmented by Hsp104

Kryndushkin

Alexandrov

Ter‐Avanesyan

et al. 2003

Journal of Biological Chemistry

432

539

View full text Add to dashboard Cite

Some proteins can change their fold from normal to a specific alternative form, called prion, which is able to catalyze this change (1). In man and animals such process causes prion diseases like Creutzfeldt-Jacob disease, bovine spongiform encephalopathy, and scrapie of sheep. A similar autocatalytic mechanism is shared by human amyloid diseases, which are noninfectious, in contrast to prion diseases (2). In yeast, there are several proteins, which can undergo prion-like structural conversion. The most studied of them are translation termination factor eRF3, also called Sup35, and Ure2 involved in regulation of nitrogen metabolism (3 was not lost (9). Hsp104 was shown to break large aggregates of denatured protein into smaller pieces (10, 11). We proposed that Hsp104 acts similarly on fiber-shaped prion polymers, thus fragmenting them into shorter polymers and increasing their number (12). This is essential for their inheritance and accelerates the prion conversion by multiplying the ends of prion polymers, where the conversion occurs. The overproduction of Hsp104 should cause excessive fragmentation, increased levels of soluble Sup35, and possibly [PSI ϩ ] loss. An alternative model proposed that Hsp104 is primarily required to facilitate the prion conversion in one or another way (13,14).These two models may be distinguished, since they make different predictions for alteration of the size of prion particles upon inhibition of the Hsp104 function. By the former model, the size should increase due to blocked fragmentation, while by the latter it should stay constant or decrease due to block of polymerization. Recent studies provided some support for the "fragmentation" model. Decrease of the Hsp104 expression caused increase in the size of Sup35 prion aggregates, suggesting decreased disaggregation by Hsp104 (15). The activity of Hsp104 is inhibited by growing yeast cells in the presence of 3-5 mM guanidine HCl (GuHCl) 1 (16). Such treatment cures efficiently [PSI ϩ ] (17) and other known yeast prions. Study of the kinetics of [PSI ϩ ] loss in the presence of GuHCl allowed concluding that it blocks replication of prion "seeds" (18,19). Thus, Hsp104 inhibition correlates with the block of fragmentation (replication) of prion particles (seeds). However, in these experiments the relation of the studied prion entities to the Sup35 polymers considered by the above models was not characterized. The prion seeds were defined genetically, but their physical nature was not studied. In the work (15) the size of

show abstract

Section: Polymers and Aggregates: Two Levels In The Structure Ofmentioning

confidence: 77%

Yeast [PSI+] Prion Aggregates Are Formed by Small Sup35 Polymers Fragmented by Hsp104

Kryndushkin

Alexandrov

Ter‐Avanesyan

et al. 2003

Journal of Biological Chemistry

432

539

View full text Add to dashboard Cite

show abstract

“…While this reflection is generally agreed to be present in dried fibers, it has been reported to be missing in hydrated fibers, suggesting that the dried fibers and hydrated cellular prion could be in different confirmations (Bousset et al 2002a(Bousset et al , 2003(Bousset et al , 2004Fernandez-Bellot et al 2002;Kishimoto et al 2004). However, two groups have found this reflection to be associated even with hydrated prion fibers (Shewmaker et al 2009a;Wang et al 2011).…”

Section: Models Of Prion Structuresmentioning

confidence: 95%

Prions in Yeast

2012

View full text Add to dashboard Cite

The concept of a prion as an infectious self-propagating protein isoform was initially proposed to explain certain mammalian diseases. It is now clear that yeast also has heritable elements transmitted via protein. Indeed, the "protein only" model of prion transmission was first proven using a yeast prion. Typically, known prions are ordered cross-b aggregates (amyloids). Recently, there has been an explosion in the number of recognized prions in yeast. Yeast continues to lead the way in understanding cellular control of prion propagation, prion structure, mechanisms of de novo prion formation, specificity of prion transmission, and the biological roles of prions. This review summarizes what has been learned from yeast prions.

show abstract

“…Total Slt2p was detected with a-GST-Slt2p antibodies, kindly provided by H. Martin and M. Molina (Universidad Complutense de Madrid, Madrid, Spain), at 1 : 2500 dilution. Fur4 and Ure2 proteins were detected using specific polyclonal antibodies at 1 : 1000 and 1 : 3000 dilutions, respectively (Silve et al, 1991;Fernandez-Bellot et al, 2002). Anti-HA 12CA5 monoclonal antibody was used at 1 : 10 000 dilution.…”

Section: Methodsmentioning

confidence: 99%

The Rho3 and Rho4 small GTPases interact functionally with Wsc1p, a cell surface sensor of the protein kinase C cell-integrity pathway in Saccharomyces cerevisiae

et al. 2006

View full text Add to dashboard Cite

Rgd1, a GTPase-activating protein, is the only known negative regulator of the Rho3 and Rho4 small GTPases in the yeast Saccharomyces cerevisiae. Rho3p and Rho4p are involved in regulating cell polarity by controlling polarized exocytosis. Co-inactivation of RGD1 and WSC1, which is a cell wall sensor-encoding gene, is lethal. Another plasma membrane sensor, Mid2p, is known to rescue the rgd1Dwsc1D synthetic lethality. It has been proposed that Wsc1p and Mid2p act upstream of the protein kinase C (PKC) pathway to function as mechanosensors of cell wall stress. Analysis of the synthetic lethal phenomenon revealed that production of activated Rho3p and Rho4p leads to lethality in wsc1D cells. Inactivation of RHO3 or RHO4 was able to rescue the rgd1Dwsc1D synthetic lethality, supporting the idea that the accumulation of GTP-bound Rho proteins, following loss of Rgd1p, is detrimental if the Wsc1 sensor is absent. In contrast, the genetic interaction between RGD1 and MID2 was not due to an accumulation of GTP-bound Rho proteins. It was proposed that simultaneous inactivation of RGD1 and WSC1 constitutively activates the PKC-mitogen-activated protein kinase (MAP kinase) pathway. Moreover, it was shown that the activity of this pathway was not involved in the synthetic lethal interaction, which suggests the existence of another mechanism. Consistent with this idea, it was found that perturbations in Rho3-mediated polarized exocytosis specifically impair the abundance and processing of Wsc1 and Mid2 proteins. Hence, it is proposed that Wsc1p participates in the regulation of a Rho3/4-dependent cellular mechanism, and that this is distinct from the role of Wsc1p in the PKC-MAP kinase pathway.

show abstract

The [URE3] phenotype: evidence for a soluble prion in yeast

Cited by 25 publications

References 21 publications

Yeast [PSI+] Prion Aggregates Are Formed by Small Sup35 Polymers Fragmented by Hsp104

Yeast [PSI+] Prion Aggregates Are Formed by Small Sup35 Polymers Fragmented by Hsp104

Prions in Yeast

The Rho3 and Rho4 small GTPases interact functionally with Wsc1p, a cell surface sensor of the protein kinase C cell-integrity pathway in Saccharomyces cerevisiae

Contact Info

Product

Resources

About