DMSO-mediated curing of several yeast prion variants involves Hsp104 expression and protein solubilization, and is decreased in several autophagy related gene (atg) mutants.

PloS One
Jane E DorweilerAnita L Manogaran

Abstract

Chaperones and autophagy are components of the protein quality control system that contribute to the management of proteins that are misfolded and aggregated. Here, we use yeast prions, which are self-perpetuating aggregating proteins, as a means to understand how these protein quality control systems influence aggregate loss. Chaperones, such as Hsp104, fragment prion aggregates to generate more prion seeds for propagation. While much is known about the role of chaperones, little is known about how other quality control systems contribute to prion propagation. We show that the aprotic solvent dimethyl sulfoxide (DMSO) cures a range of [PSI+] prion variants, which are related to several misfolded aggregated conformations of the Sup35 protein. Our studies show that DMSO-mediated curing is quicker and more efficient than guanidine hydrochloride, a prion curing agent that inactivates the Hsp104 chaperone. Instead, DMSO appears to induce Hsp104 expression. Using the yTRAP system, a recently developed transcriptional reporting system for tracking protein solubility, we found that DMSO also rapidly induces the accumulation of soluble Sup35 protein, suggesting a potential link between Hsp104 expression and disassembly of Sup35 from th...Continue Reading

References

Sep 1, 1988·Yeast·B S CoxC S McLaughlin
Jan 5, 2000·Proceedings of the National Academy of Sciences of the United States of America·S S EaglestoneM F Tuite
Jun 21, 2001·Molecular and Cellular Biology·R D WegrzynY O Chernoff
Jul 9, 2002·Molecular and Cellular Biology·Frédérique NessMick F Tuite
Sep 26, 2003·The Journal of Biological Chemistry·Dmitry S KryndushkinVitaly V Kushnirov
Jul 1, 2006·Nature·Motomasa TanakaJonathan S Weissman
Jan 27, 2007·PLoS Biology·Prasanna Satpute-KrishnanTricia R Serio
Oct 6, 2009·Nature Cell Biology·Tobias EisenbergFrank Madeo
Mar 12, 2011·Journal of Molecular Biology·Gary P NewnamYury O Chernoff
Jun 1, 2011·PLoS Genetics·Anita L ManogaranSusan W Liebman
Nov 15, 2011·The Journal of Biological Chemistry·Christopher W Helsen, John R Glover
Jun 19, 2013·Journal of Molecular Biology·Jaya Sharma, Susan W Liebman
Dec 4, 2014·The EMBO Journal·Hanghang HuangEiichiro Fukusaki
Mar 19, 2015·Annual Review of Biochemistry·Johnathan Labbadia, Richard I Morimoto
Mar 3, 2017·Scientific Reports·Jaya SharmaAnita L Manogaran
Oct 24, 2017·Cell·Gregory A NewbyAhmad S Khalil

❮ Previous
Next ❯

Citations

Sep 11, 2020·International Journal of Molecular Sciences·Lois E GreeneXiaohong Zhao
Jul 29, 2021·Current Genetics·Reed B WicknerMadaleine Niznikiewicz

❮ Previous
Next ❯

Methods Mentioned

BETA
environmental stress
flow cytometry
PCR

Related Concepts

Related Feeds

ATG proteins

The discovery of autophagy-related ('ATG') proteins in the 1990s greatly advanced the mechanistic understanding of autophagy and clarified the fact that autophagy serves important roles in various biological processes.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms