scholarly journals Cellular sequestrases maintain basal Hsp70 capacity ensuring balanced proteostasis

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Chi-ting Ho ◽  
Tomas Grousl ◽  
Oren Shatz ◽  
Areeb Jawed ◽  
Carmen Ruger-Herreros ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Quality Control ◽  
Heat Shock ◽  
Misfolded Proteins ◽  
Control Network ◽  
Stress Recovery ◽  
Degradation Pathways ◽  
Misfolded Protein ◽  
Shock Proteins

Abstract Maintenance of cellular proteostasis is achieved by a multi-layered quality control network, which counteracts the accumulation of misfolded proteins by refolding and degradation pathways. The organized sequestration of misfolded proteins, actively promoted by cellular sequestrases, represents a third strategy of quality control. Here we determine the role of sequestration within the proteostasis network in Saccharomyces cerevisiae and the mechanism by which it occurs. The Hsp42 and Btn2 sequestrases are functionally intertwined with the refolding activity of the Hsp70 system. Sequestration of misfolded proteins by Hsp42 and Btn2 prevents proteostasis collapse and viability loss in cells with limited Hsp70 capacity, likely by shielding Hsp70 from misfolded protein overload. Btn2 has chaperone and sequestrase activity and shares features with small heat shock proteins. During stress recovery Btn2 recruits the Hsp70-Hsp104 disaggregase by directly interacting with the Hsp70 co-chaperone Sis1, thereby shunting sequestered proteins to the refolding pathway.

scholarly journals Hsp42 is required for sequestration of protein aggregates into deposition sites in Saccharomyces cerevisiae

2011 ◽  
Vol 195 (4) ◽  
pp. 617-629 ◽  
Author(s):  
Sebastian Specht ◽  
Stephanie B.M. Miller ◽  
Axel Mogk ◽  
Bernd Bukau
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Quality Control ◽  
Heat Stress ◽  
Heat Shock ◽  
Misfolded Proteins ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Cellular Machinery ◽  
Shock Proteins ◽  
Amino Terminal Domain

The aggregation of proteins inside cells is an organized process with cytoprotective function. In Saccharomyces cerevisiae, aggregating proteins are spatially sequestered to either juxtanuclear or peripheral sites, which target distinct quality control pathways for refolding and degradation. The cellular machinery driving the sequestration of misfolded proteins to these sites is unknown. In this paper, we show that one of the two small heat shock proteins of yeast, Hsp42, is essential for the formation of peripheral aggregates during physiological heat stress. Hsp42 preferentially localizes to peripheral aggregates but is largely absent from juxtanuclear aggregates, which still form in hsp42Δ cells. Transferring the amino-terminal domain of Hsp42 to Hsp26, which does not participate in aggregate sorting, enables Hsp26 to replace Hsp42 function. Our data suggest that Hsp42 acts via its amino-terminal domain to coaggregate with misfolded proteins and perhaps link such complexes to further sorting factors.

scholarly journals Alzheimer Cells on Their Way to Derailment Show Selective Changes in Protein Quality Control Network

2020 ◽  
Vol 7 ◽  
Author(s):  
Margreet B. Koopman ◽  
Stefan G. D. Rüdiger
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Quality Control ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Brain Regions ◽  
Control Network ◽  
Shock Proteins

Alzheimer’s Disease is driven by protein aggregation and is characterized by accumulation of Tau protein into neurofibrillary tangles. In healthy neurons the cellular protein quality control is successfully in charge of protein folding, which raises the question to which extent this control is disturbed in disease. Here, we describe that brain cells in Alzheimer’s Disease show very specific derailment of the protein quality control network. We performed a meta-analysis on the Alzheimer’s Disease Proteome database, which provides a quantitative assessment of disease-related proteome changes in six brain regions in comparison to age-matched controls. We noted that levels of all paralogs of the conserved Hsp90 chaperone family are reduced, while most other chaperones – or their regulatory co-chaperones - do not change in disease. The notable exception is a select group consisting of the stress inducible HSP70, its nucleotide exchange factor BAG3 – which links the Hsp70 system to autophagy - and neuronal small heat shock proteins, which are upregulated in disease. They are all members of a cascade controlled in the stress response, channeling proteins towards a pathway of chaperone assisted selective autophagy. Together, our analysis reveals that in an Alzheimer’s brain, with exception of Hsp90, the players of the protein quality control are still present in full strength, even in brain regions most severely affected in disease. The specific upregulation of small heat shock proteins and HSP70:BAG3, ubiquitous in all brain areas analyzed, may represent a last, unsuccessful attempt to advert cell death.

scholarly journals Alzheimer cells on their way to derailment show selective changes in protein quality control network

2020 ◽  
Author(s):  
Margreet B. Koopman ◽  
Stefan G.D Rüdiger
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Quality Control ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Brain Regions ◽  
Control Network ◽  
Shock Proteins

Alzheimer’s Disease is driven by protein aggregation and is characterised by accumulation of Tau protein into neurofibrillary tangles. In healthy neurons the cellular protein quality control is successfully in charge of protein folding, which raises the question to which extent this control is disturbed in disease. Here we describe that brain cells in Alzheimer’s Disease show very specific derailment of the protein quality control network. We performed a meta-analysis on the Alzheimer’s Disease Proteasome database, which provides a quantitative assessment of disease-related proteome changes in six brain regions in comparison with age-matched controls. We noted that levels of all paralogues of the conserved Hsp90 chaperone family are reduced, while most other chaperones – or their regulatory co-chaperones – do not change in disease. The notable exception is a select group consisting of the stress inducible HSP70, its nucleotide exchange factor BAG3 – which links the Hsp70 system to autophagy – and neuronal small heat shock proteins, which are upregulated in disease. They are all members of a cascade controlled in the stress response, channelling proteins towards a pathway of chaperone assisted selective autophagy. Together, our analysis reveals that in an Alzheimer’s brain, with exception of Hsp90, the players of the protein quality control are still present in full strength, even in brain regions most severely affected in disease. The specific upregulation of small heat shock proteins and HSP70:BAG3, ubiquitous in all brain areas analysed, may represent a last, unsuccessful attempt to advert neuronal cell death.

scholarly journals hsp26 of Saccharomyces cerevisiae is related to the superfamily of small heat shock proteins but is without a demonstrable function.

1989 ◽  
Vol 9 (11) ◽  
pp. 5265-5271 ◽  
Author(s):  
R E Susek ◽  
S L Lindquist
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Mutational Analysis ◽  
Small Heat Shock Protein ◽  
Major Effect ◽  
Selfish Dna ◽  
Dna Elements ◽  
Cloned Gene ◽  
Shock Proteins

Analysis of the cloned gene confirms that hsp26 of Saccharomyces cerevisiae is a member of the small heat shock protein superfamily. Previous mutational analysis failed to demonstrate any function for the protein. Further experiments presented here demonstrate that hsp26 has no obvious regulatory role and no major effect on thermotolerance. It is possible that the small heat shock protein genes originated as primitive viral or selfish DNA elements.

Heat shock response of Saccharomyces cerevisiae mutants altered in cyclic AMP-dependent protein phosphorylation

1987 ◽  
Vol 7 (1) ◽  
pp. 244-250
Author(s):  
D Y Shin ◽  
K Matsumoto ◽  
H Iida ◽  
I Uno ◽  
T Ishikawa
Keyword(s):  
Heat Treatment ◽  
Saccharomyces Cerevisiae ◽  
Heat Shock ◽  
Cyclic Amp ◽  
Heat Shock Proteins ◽  
Temperature Shift ◽  
G1 Phase ◽  
Shock Response ◽  
Dependent Protein ◽  
Shock Proteins

When Saccharomyces cerevisiae cells grown at 23 degrees C were transferred to 36 degrees C, they initiated synthesis of heat shock proteins, acquired thermotolerance to a lethal heat treatment given after the temperature shift, and arrested their growth transiently at the G1 phase of the cell division cycle. The bcy1 mutant which resulted in production of cyclic AMP (cAMP)-independent protein kinase did not synthesize the three heat shock proteins hsp72A, hsp72B, and hsp41 after the temperature shift. The bcy1 cells failed to acquire thermotolerance to the lethal heat treatment and were not arrested at the G1 phase after the temperature shift. In contrast, the cyr1-2 mutant, which produced a low level of cAMP, constitutively produced three heat shock proteins and four other proteins without the temperature shift and was resistant to the lethal heat treatment. The results suggest that a decrease in the level of cAMP-dependent protein phosphorylation results in the heat shock response, including elevated synthesis of three heat shock proteins, acquisition of thermotolerance, and transient arrest of the cell cycle.

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