Dual roles for ATP in the regulation of phase separated protein aggregates in Xenopus oocyte nucleoli
For many proteins, aggregation is one part of a structural equilibrium that can occur. Balancing productive aggregation versus pathogenic aggregation that leads to toxicity is critical and known to involve adenosine triphosphate (ATP) dependent action of chaperones and disaggregases. Recently a seco...
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doaj-127c8da884a347a8aa3124bbb6caff632021-05-05T16:01:37ZengeLife Sciences Publications LtdeLife2050-084X2018-07-01710.7554/eLife.35224Dual roles for ATP in the regulation of phase separated protein aggregates in Xenopus oocyte nucleoliMichael H Hayes0Elizabeth H Peuchen1Norman J Dovichi2Daniel L Weeks3https://orcid.org/0000-0002-4977-2410Molecular Medicine Doctoral Program, University of Iowa Carver College of Medicine, Iowa City, United StatesDepartment of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, United StatesDepartment of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, United StatesMolecular Medicine Doctoral Program, University of Iowa Carver College of Medicine, Iowa City, United States; Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, United StatesFor many proteins, aggregation is one part of a structural equilibrium that can occur. Balancing productive aggregation versus pathogenic aggregation that leads to toxicity is critical and known to involve adenosine triphosphate (ATP) dependent action of chaperones and disaggregases. Recently a second activity of ATP was identified, that of a hydrotrope which, independent of hydrolysis, was sufficient to solubilize aggregated proteins in vitro. This novel function of ATP was postulated to help regulate proteostasis in vivo. We tested this hypothesis on aggregates found in Xenopus oocyte nucleoli. Our results indicate that ATP has dual roles in the maintenance of protein solubility. We provide evidence of endogenous hydrotropic action of ATP but show that hydrotropic solubilization of nucleolar aggregates is preceded by a destabilizing event. Destabilization is accomplished through an energy dependent process, reliant upon ATP and one or more soluble nuclear factors, or by disruption of a co-aggregate like RNA.https://elifesciences.org/articles/35224protein aggregationnucleolusnucleusoocyteATP |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Michael H Hayes Elizabeth H Peuchen Norman J Dovichi Daniel L Weeks |
spellingShingle |
Michael H Hayes Elizabeth H Peuchen Norman J Dovichi Daniel L Weeks Dual roles for ATP in the regulation of phase separated protein aggregates in Xenopus oocyte nucleoli eLife protein aggregation nucleolus nucleus oocyte ATP |
author_facet |
Michael H Hayes Elizabeth H Peuchen Norman J Dovichi Daniel L Weeks |
author_sort |
Michael H Hayes |
title |
Dual roles for ATP in the regulation of phase separated protein aggregates in Xenopus oocyte nucleoli |
title_short |
Dual roles for ATP in the regulation of phase separated protein aggregates in Xenopus oocyte nucleoli |
title_full |
Dual roles for ATP in the regulation of phase separated protein aggregates in Xenopus oocyte nucleoli |
title_fullStr |
Dual roles for ATP in the regulation of phase separated protein aggregates in Xenopus oocyte nucleoli |
title_full_unstemmed |
Dual roles for ATP in the regulation of phase separated protein aggregates in Xenopus oocyte nucleoli |
title_sort |
dual roles for atp in the regulation of phase separated protein aggregates in xenopus oocyte nucleoli |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2018-07-01 |
description |
For many proteins, aggregation is one part of a structural equilibrium that can occur. Balancing productive aggregation versus pathogenic aggregation that leads to toxicity is critical and known to involve adenosine triphosphate (ATP) dependent action of chaperones and disaggregases. Recently a second activity of ATP was identified, that of a hydrotrope which, independent of hydrolysis, was sufficient to solubilize aggregated proteins in vitro. This novel function of ATP was postulated to help regulate proteostasis in vivo. We tested this hypothesis on aggregates found in Xenopus oocyte nucleoli. Our results indicate that ATP has dual roles in the maintenance of protein solubility. We provide evidence of endogenous hydrotropic action of ATP but show that hydrotropic solubilization of nucleolar aggregates is preceded by a destabilizing event. Destabilization is accomplished through an energy dependent process, reliant upon ATP and one or more soluble nuclear factors, or by disruption of a co-aggregate like RNA. |
topic |
protein aggregation nucleolus nucleus oocyte ATP |
url |
https://elifesciences.org/articles/35224 |
work_keys_str_mv |
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