Dual roles for ATP in the regulation of phase separated protein aggregates in Xenopus oocyte nucleoli

Michael H Hayes; Elizabeth H Peuchen; Norman J Dovichi; Daniel L Weeks

doi:10.7554/eLife.35224

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Dual roles for ATP in the regulation of phase separated protein aggregates in Xenopus oocyte nucleoli

Journal article

Open access

Peer reviewed

Dual roles for ATP in the regulation of phase separated protein aggregates in Xenopus oocyte nucleoli

Michael H Hayes, Elizabeth H Peuchen, Norman J Dovichi and Daniel L Weeks

eLife, Vol.7, e35224

07/17/2018

DOI: 10.7554/eLife.35224

PMCID: PMC6050040

PMID: 30015615

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Abstract

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 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.

Protein Aggregates

Green Fluorescent Proteins - metabolism

Guanosine Triphosphate - pharmacology

Oocytes - metabolism

Solubility

Hydrolysis

Adenylyl Imidodiphosphate - pharmacology

Animals

Ribonuclease, Pancreatic - metabolism

Models, Biological

Xenopus laevis - metabolism

Adenosine Triphosphate - metabolism

Cell Nucleolus - metabolism

Cell Nucleolus - drug effects

Oocytes - drug effects

Diffusion

Details

Title: Subtitle: Dual roles for ATP in the regulation of phase separated protein aggregates in Xenopus oocyte nucleoli
Creators: Michael H Hayes - Molecular Medicine Doctoral Program, University of Iowa Carver College of Medicine, Iowa City, United States
Elizabeth H Peuchen - Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, United States
Norman J Dovichi - Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, United States
Daniel L Weeks - Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, United States
Resource Type: Journal article
Publication Details: eLife, Vol.7, e35224
DOI: 10.7554/eLife.35224
PMID: 30015615
PMCID: PMC6050040
NLM abbreviation: Elife
ISSN: 2050-084X
eISSN: 2050-084X
Publisher: England
Grant note: R01 HD084399 / NICHD NIH HHS R01 GM096767 / NIGMS NIH HHS R01GM096767 / NIGMS NIH HHS Medical Scientist Training Program / NIGMS NIH HHS R01HD084399 / NIGMS NIH HHS T32 GM007337 / NIGMS NIH HHS
Language: English
Date published: 07/17/2018
Academic Unit: Stead Family Department of Pediatrics; Biochemistry and Molecular Biology
Record Identifier: 9984025247802771

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