scholarly journals Influence of Hsp70s and their regulators on yeast prion propagation

Prion ◽  
2009 ◽  
Vol 3 (2) ◽  
pp. 65-73 ◽  
Author(s):  
Daniel C. Masison ◽  
P. Aaron Kirkland ◽  
Deepak Sharma
Keyword(s):  
Yeast Prion ◽  
Prion Propagation

Huntingtin Polyglutamine Fragments Are a Substrate for Hsp104 in Yeast

2021 ◽  
Author(s):  
Nicole J. Wayne ◽  
Katherine E. Dembny ◽  
Tyler Pease ◽  
Farrin Saba ◽  
Xiaohong Zhao ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Essential Role ◽  
Marked Effect ◽  
Yeast Prion ◽  
Rich Region ◽  
Polyglutamine Repeat ◽  
Prion Propagation

The aggregation of huntingtin fragments with expanded polyglutamine repeat regions (HttpolyQ) that cause Huntington’s disease depends on the presence of a prion with an amyloid conformation in yeast. As a result of this relationship, HttpolyQ aggregation indirectly depends on Hsp104 due to its essential role in prion propagation. We find that HttQ103 aggregation is directly affected by Hsp104 with and without the presence of [ RNQ + ] and [ PSI + ] prions. When we inactivate Hsp104 in the presence of prion, yeast have only one or a few large HttQ103 aggregates rather than numerous smaller aggregates. When we inactivate Hsp104 in the absence of prion, there is no significant aggregation of HttQ103; whereas with active Hsp104, HttQ103 aggregates slowly accumulate due to the severing of spontaneously nucleated aggregates by Hsp104. We do not observe either effect with HttQ103P, which has a polyproline-rich region downstream of the polyglutamine region, because HttQ103P does not spontaneously nucleate and Hsp104 does not efficiently sever the prion-nucleated HttQ103P aggregates. Therefore, the only role of Hsp104 in HttQ103P aggregation is to propagate yeast prion. In conclusion, because Hsp104 efficiently severs the HttQ103 aggregates, but not HttQ103P aggregates, it has a marked effect on the aggregation of HttQ103, but not HttQ103P.

scholarly journals Mutational Analysis of Sse1 (Hsp110) Suggests an Integral Role for this Chaperone in Yeast Prion Propagation In Vivo

2013 ◽  
Vol 3 (8) ◽  
pp. 1409-1418 ◽  
Author(s):  
Ciara Moran ◽  
Gemma K. Kinsella ◽  
Zai-Rong Zhang ◽  
Sarah Perrett ◽  
Gary W. Jones
Keyword(s):  
Mutational Analysis ◽  
Yeast Prion ◽  
Prion Propagation ◽  
Integral Role

scholarly journals Amyloid conformation-dependent disaggregation revealed by a reconstituted yeast prion system

2020 ◽  
Author(s):  
Motomasa Tanaka ◽  
Yoshiko Nakagawa ◽  
Howard C.-H. Shen ◽  
Shinju Sugiyama ◽  
Yuri Tomabechi ◽  
...  
Keyword(s):  
Single Molecule ◽  
Amyloid Fibrils ◽  
Yeast Prion ◽  
Experimental Systems ◽  
Prion Propagation ◽  
Therapeutic Development ◽  
Fundamental Biological Process ◽  
Physical Foundation

Abstract Disaggregation of amyloid fibrils is a fundamental biological process required for amyloid propagation. However, due to the lack of experimental systems, the molecular mechanism of how amyloid is disaggregated by cellular factors remains poorly understood. Here, we established a robust, in vitro reconstituted system of yeast prion propagation and found that Hsp104, Ssa1, and Sis1 chaperones are essential for efficient disaggregation of Sup35 amyloid. Real-time imaging of single-molecule fluorescence coupled with the reconstitution system revealed that amyloid disaggregation is achieved by ordered, timely binding of the chaperones to the amyloid. Remarkably, we uncovered two distinct, prion strain conformation-dependent modes of disaggregation, fragmentation and dissolution. We characterized distinct chaperon dynamics in each mode and found that transient, repeated binding of Hsp104 to the same site of amyloid results in fragmentation. These findings provide a physical foundation for otherwise puzzling in vivo observations and for therapeutic development for amyloid-associated neurodegenerative diseases.

scholarly journals Regulation of the Hsp104 Middle Domain Activity Is Critical for Yeast Prion Propagation

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e87521 ◽  
Author(s):  
Jennifer E. Dulle ◽  
Kevin C. Stein ◽  
Heather L. True
Keyword(s):  
Yeast Prion ◽  
Middle Domain ◽  
Prion Propagation

scholarly journals Analysis of the Generation and Segregation of Propagons: Entities That Propagate the [PSI+] Prion in Yeast

Genetics ◽  
2003 ◽  
Vol 165 (1) ◽  
pp. 23-33 ◽  
Author(s):  
Brian Cox ◽  
Frederique Ness ◽  
Mick Tuite
Keyword(s):  
Guanidine Hydrochloride ◽  
Normal Growth ◽  
S Phase ◽  
Clonal Variation ◽  
Yeast Prion ◽  
Yeast Strains ◽  
Prion Propagation ◽  
Mother Cells ◽  
Different Cultures ◽  
Kinetics Of

Abstract The propagation of the prion form of the yeast Sup35p protein, the so-called [PSI+] determinant, involves the generation and partition of a small number of particulate determinants that we propose calling “propagons.” The numbers of propagons in [PSI+] cells can be inferred from the kinetics of elimination of [PSI+] during growth in the presence of a low concentration of guanidine hydrochloride (GdnHCl). Using this and an alternative method of counting the numbers of propagons, we demonstrate considerable clonal variation in the apparent numbers of propagons between different [PSI+] yeast strains, between different cultures of the same [PSI+] yeast strain, and between different cells of the same [PSI+] culture. We provide further evidence that propagon generation is blocked by growth in GdnHCl and that it is largely confined to the S phase of the cell cycle. In addition, we show that at low propagon number there is a bias toward retention of propagons in mother cells and that production of new propagons is very rapid when cells with depleted numbers of propagons are rescued into normal growth medium. The implications of our findings with respect to yeast prion propagation mechanisms are discussed.

scholarly journals Point mutations affecting yeast prion propagation change the structure of its amyloid fibrils

2020 ◽  
Vol 314 ◽  
pp. 113618
Author(s):  
Anna I. Sulatskaya ◽  
Stanislav A. Bondarev ◽  
Maksim I. Sulatsky ◽  
Nina P. Trubitsina ◽  
Mikhail V. Belousov ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Point Mutations ◽  
Yeast Prion ◽  
Prion Propagation
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