10th Anniversary of Biology: Amyloid Interaction in Regulation of Protein Function, Prion Propagation, and Cell Death

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Biotechnology".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 7300

Special Issue Editor

1. CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne BP64182, F-31077 Toulouse, France
2. UPS, IPBS, Université de Toulouse, F-31077 Toulouse, France
3. LCC UPR8241 CNRS, F-31400 Toulouse, France
Interests: prion; amyloid; necroptosis; MLKL RIP kinase; podospora
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Special Issue Information

Dear Colleagues,

The year 2021 marks the 10th anniversary of Biology, a peer-reviewed open access journal on biological sciences. Biology has published more than 1200 papers from more than 8300 authors. We are grateful to every author, reviewer, and academic editor whose support has made us where we are today.

To mark this significant milestone, a Special Issue entitled “10th Anniversary of Biology: Amyloid Interaction in Regulation of Protein Function, Prion Propagation, and Cell Death” is being launched. Amyloid aggregation has been involved in severe neurodegenerative disease as well as in the regulation of cell functions. Physical properties of amyloid fibrils are useful for natural biofilms and are utilized for artificial nanotube elaboration. However, they also form membrane pores leading to cellular lysis. How can amyloid proteins govern cell viability through hydrophobic interactions, and how do cells deal with the formation of toxic aggregates? These are the questions that this review series aims to answer. Several aspects of amyloid aggregation, such as structural characterizations, the spread of yeast prions, cellular necroptosis, and neurodegeneration, will be examined. Recent interest in anti-prion systems (such as chemical or natural chaperones) and in the viral ability to block necroptosis by targeting amyloid interaction will add a therapeutic perspective to this series.

Dr. Marie‑Lise Maddelein
Guest Editor

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Keywords

  • prion
  • amyloid
  • yeast
  • necroptose
  • fungi
  • chaperone
  • neurodegeneration
  • Alzheimer’s
  • infectious propagation
  • anti-prion system

Published Papers (4 papers)

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Research

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17 pages, 2789 KiB  
Article
Human J-Domain Protein DnaJB6 Protects Yeast from [PSI+] Prion Toxicity
by Richard E. Dolder III, Jyotsna Kumar, Michael Reidy and Daniel C. Masison
Biology 2022, 11(12), 1846; https://0-doi-org.brum.beds.ac.uk/10.3390/biology11121846 - 18 Dec 2022
Viewed by 1821
Abstract
Human J-domain protein (JDP) DnaJB6 has a broad and potent activity that prevents formation of amyloid by polypeptides such as polyglutamine, A-beta, and alpha-synuclein, related to Huntington’s, Alzheimer’s, and Parkinson’s diseases, respectively. In yeast, amyloid-based [PSI+] prions, which rely on [...] Read more.
Human J-domain protein (JDP) DnaJB6 has a broad and potent activity that prevents formation of amyloid by polypeptides such as polyglutamine, A-beta, and alpha-synuclein, related to Huntington’s, Alzheimer’s, and Parkinson’s diseases, respectively. In yeast, amyloid-based [PSI+] prions, which rely on the related JDP Sis1 for replication, have a latent toxicity that is exposed by reducing Sis1 function. Anti-amyloid activity of DnaJB6 is very effective against weak [PSI+] prions and the Sup35 amyloid that composes them, but ineffective against strong [PSI+] prions composed of structurally different amyloid of the same Sup35. This difference reveals limitations of DnaJB6 that have implications regarding its therapeutic use for amyloid disease. Here, we find that when Sis1 function is reduced, DnaJB6 represses toxicity of strong [PSI+] prions and inhibits their propagation. Both Sis1 and DnaJB6, which are regulators of protein chaperone Hsp70, counteract the toxicity by reducing excessive incorporation of the essential Sup35 into prion aggregates. However, while Sis1 apparently requires interaction with Hsp70 to detoxify [PSI+], DnaJB6 counteracts prion toxicity by a different, Hsp70-independent mechanism. Full article
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15 pages, 20026 KiB  
Article
Processing of Fluorescent Proteins May Prevent Detection of Prion Particles in [PSI+] Cells
by Andrew G. Matveenko, Varvara E. Ryzhkova, Natalia A. Zaytseva, Lavrentii G. Danilov, Anastasia S. Mikhailichenko, Yury A. Barbitoff and Galina A. Zhouravleva
Biology 2022, 11(12), 1688; https://0-doi-org.brum.beds.ac.uk/10.3390/biology11121688 - 22 Nov 2022
Cited by 1 | Viewed by 1582
Abstract
Yeast is a convenient model for studying protein aggregation as it is known to propagate amyloid prions. [PSI+] is the prion form of the release factor eRF3 (Sup35). Aggregated Sup35 causes defects in termination of translation, which results in nonsense [...] Read more.
Yeast is a convenient model for studying protein aggregation as it is known to propagate amyloid prions. [PSI+] is the prion form of the release factor eRF3 (Sup35). Aggregated Sup35 causes defects in termination of translation, which results in nonsense suppression in strains carrying premature stop codons. N-terminal and middle (M) domains of Sup35 are necessary and sufficient for maintaining [PSI+] in cells while preserving the prion strain’s properties. For this reason, Sup35NM fused to fluorescent proteins is often used for [PSI+] detection and investigation. However, we found that in such chimeric constructs, not all fluorescent proteins allow the reliable detection of Sup35 aggregates. Particularly, transient overproduction of Sup35NM-mCherry resulted in a diffuse fluorescent pattern in the [PSI+] cells, while no loss of prions and no effect on the Sup35NM prion properties could be observed. This effect was reproduced in various unrelated strain backgrounds and prion variants. In contrast, Sup35NM fused to another red fluorescent protein, TagRFP-T, allowed the detection of [PSI+] aggregates. Analysis of protein lysates showed that Sup35NM-mCherry is actively degraded in the cell. This degradation was not caused by vacuolar proteases and the ubiquitin-proteasomal system implicated in the Sup35 processing. Even though the intensity of this proteolysis was higher than that of Sup35NM-GFP, it was roughly the same as in the case of Sup35NM-TagRFP-T. Thus, it is possible that, in contrast to TagRFP-T, degradation products of Sup35NM-mCherry still preserve their fluorescent properties while losing the ability to decorate pre-existing Sup35 aggregates. This results in diffuse fluorescence despite the presence of the prion aggregates in the cell. Thus, tagging with fluorescent proteins should be used with caution, as such proteolysis may increase the rate of false-negative results when detecting prion-bearing cells. Full article
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Review

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15 pages, 611 KiB  
Review
J Proteins Counteract Amyloid Propagation and Toxicity in Yeast
by Daniel C. Masison, Michael Reidy and Jyotsna Kumar
Biology 2022, 11(9), 1292; https://0-doi-org.brum.beds.ac.uk/10.3390/biology11091292 - 30 Aug 2022
Cited by 1 | Viewed by 1462
Abstract
The accumulation of misfolded proteins as amyloids is associated with pathology in dozens of debilitating human disorders, including diabetes, Alzheimer’s, Parkinson’s, and Huntington’s diseases. Expressing human amyloid-forming proteins in yeast is toxic, and yeast prions that propagate as infectious amyloid forms of cellular [...] Read more.
The accumulation of misfolded proteins as amyloids is associated with pathology in dozens of debilitating human disorders, including diabetes, Alzheimer’s, Parkinson’s, and Huntington’s diseases. Expressing human amyloid-forming proteins in yeast is toxic, and yeast prions that propagate as infectious amyloid forms of cellular proteins are also harmful. The yeast system, which has been useful for studying amyloids and their toxic effects, has provided much insight into how amyloids affect cells and how cells respond to them. Given that an amyloid is a protein folding problem, it is unsurprising that the factors found to counteract the propagation or toxicity of amyloids in yeast involve protein quality control. Here, we discuss such factors with an emphasis on J-domain proteins (JDPs), which are the most highly abundant and diverse regulators of Hsp70 chaperones. The anti-amyloid effects of JDPs can be direct or require interaction with Hsp70. Full article
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14 pages, 1319 KiB  
Review
Anti-Prion Systems Block Prion Transmission, Attenuate Prion Generation, Cure Most Prions as They Arise and Limit Prion-Induced Pathology in Saccharomyces cerevisiae
by Reed B. Wickner, Herman K. Edskes, Moonil Son and Songsong Wu
Biology 2022, 11(9), 1266; https://0-doi-org.brum.beds.ac.uk/10.3390/biology11091266 - 26 Aug 2022
Cited by 1 | Viewed by 1769
Abstract
All variants of the yeast prions [PSI+] and [URE3] are detrimental to their hosts, as shown by the dramatic slowing of growth (or even lethality) of a majority, by the rare occurrence in wild isolates of even the mildest variants and by the [...] Read more.
All variants of the yeast prions [PSI+] and [URE3] are detrimental to their hosts, as shown by the dramatic slowing of growth (or even lethality) of a majority, by the rare occurrence in wild isolates of even the mildest variants and by the absence of reproducible benefits of these prions. To deal with the prion problem, the host has evolved an array of anti-prion systems, acting in normal cells (without overproduction or deficiency of any component) to block prion transmission from other cells, to lower the rates of spontaneous prion generation, to cure most prions as they arise and to limit the damage caused by those variants that manage to elude these (necessarily) imperfect defenses. Here we review the properties of prion protein sequence polymorphisms Btn2, Cur1, Hsp104, Upf1,2,3, ribosome-associated chaperones, inositol polyphosphates, Sis1 and Lug1, which are responsible for these anti-prion effects. We recently showed that the combined action of ribosome-associated chaperones, nonsense-mediated decay factors and the Hsp104 disaggregase lower the frequency of [PSI+] appearance as much as 5000-fold. Moreover, while Btn2 and Cur1 are anti-prion factors against [URE3] and an unrelated artificial prion, they promote [PSI+] prion generation and propagation. Full article
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