scholarly journals The Role of the Hsp40 Chaperone Sis1 in Yeast Prion Propagation

10.5772/66449 ◽  
2017 ◽  
Author(s):  
Michael Reidy
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 Role of Hsp104 in the Propagation and Inheritance of the [Het-s] Prion

2007 ◽  
Vol 18 (12) ◽  
pp. 4803-4812 ◽  
Author(s):  
Laurent Malato ◽  
Suzana Dos Reis ◽  
Laura Benkemoun ◽  
Raimon Sabaté ◽  
Sven J. Saupe
Keyword(s):  
Meiotic Drive ◽  
Protein Aggregates ◽  
Propagation Rate ◽  
Podospora Anserina ◽  
Wild Type ◽  
Prion Propagation ◽  
Meiotic Instability

The chaperones of the ClpB/HSP100 family play a central role in thermotolerance in bacteria, plants, and fungi by ensuring solubilization of heat-induced protein aggregates. In addition in yeast, Hsp104 was found to be required for prion propagation. Herein, we analyze the role of Podospora anserina Hsp104 (PaHsp104) in the formation and propagation of the [Het-s] prion. We show that ΔPaHsp104 strains propagate [Het-s], making [Het-s] the first native fungal prion to be propagated in the absence of Hsp104. Nevertheless, we found that [Het-s]-propagon numbers, propagation rate, and spontaneous emergence are reduced in a ΔPaHsp104 background. In addition, inactivation of PaHsp104 leads to severe meiotic instability of [Het-s] and abolishes its meiotic drive activity. Finally, we show that ΔPaHSP104 strains are less susceptible than wild type to infection by exogenous recombinant HET-s(218–289) prion amyloids. Like [URE3] and [PIN+] in yeast but unlike [PSI+], [Het-s] is not cured by constitutive PaHsp104 overexpression. The observed effects of PaHsp104 inactivation are consistent with the described role of Hsp104 in prion aggregate shearing in yeast. However, Hsp104-dependency appears less stringent in P. anserina than in yeast; presumably because in Podospora prion propagation occurs in a syncitium.

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 Elucidating the role of cofactors in mammalian prion propagation

Prion ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. 100-105 ◽  
Author(s):  
Surachai Supattapone
Keyword(s):  
Prion Propagation

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

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 Prion Propagation: The Role of Protein Dynamics

Prion ◽  
2007 ◽  
Vol 1 (1) ◽  
pp. 36-43 ◽  
Author(s):  
John A. Pezza ◽  
Tricia R. Serio
Keyword(s):  
Protein Dynamics ◽  
Prion Propagation
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