The nucleolus functions as a phase-separated protein quality control compartment

doi:10.1126/science.aaw9157

. 2019 Jul 26;365(6451):342-347.

doi: 10.1126/science.aaw9157. Epub 2019 Jul 11.

The nucleolus functions as a phase-separated protein quality control compartment

F Frottin¹, F Schueder^{2

3}, S Tiwary⁴, R Gupta¹, R Körner¹, T Schlichthaerle^{2

3}, J Cox⁴, R Jungmann^{5

3}, F U Hartl^{6

7}, M S Hipp^{6

7}

Affiliations

¹ Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany.
² Research Group "Molecular Imaging and Bionanotechnology," Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany.
³ Faculty of Physics and Center for Nanoscience, Ludwig Maximilian University, D-80539 Munich, Germany.
⁴ Research Group "Computational Systems Biochemistry," Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany.
⁵ Research Group "Molecular Imaging and Bionanotechnology," Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany. uhartl@biochem.mpg.de hipp@biochem.mpg.de jungmann@biochem.mpg.de.
⁶ Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany. uhartl@biochem.mpg.de hipp@biochem.mpg.de jungmann@biochem.mpg.de.
⁷ Munich Cluster for Systems Neurology (SyNergy), D-80336 Munich, Germany.

PMID: 31296649
DOI: 10.1126/science.aaw9157

The nucleolus functions as a phase-separated protein quality control compartment

F Frottin et al. Science. 2019.

. 2019 Jul 26;365(6451):342-347.

doi: 10.1126/science.aaw9157. Epub 2019 Jul 11.

Authors

F Frottin¹, F Schueder^{2

3}, S Tiwary⁴, R Gupta¹, R Körner¹, T Schlichthaerle^{2

3}, J Cox⁴, R Jungmann^{5

3}, F U Hartl^{6

7}, M S Hipp^{6

7}

Affiliations

¹ Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany.
² Research Group "Molecular Imaging and Bionanotechnology," Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany.
³ Faculty of Physics and Center for Nanoscience, Ludwig Maximilian University, D-80539 Munich, Germany.
⁴ Research Group "Computational Systems Biochemistry," Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany.
⁵ Research Group "Molecular Imaging and Bionanotechnology," Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany. uhartl@biochem.mpg.de hipp@biochem.mpg.de jungmann@biochem.mpg.de.
⁶ Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany. uhartl@biochem.mpg.de hipp@biochem.mpg.de jungmann@biochem.mpg.de.
⁷ Munich Cluster for Systems Neurology (SyNergy), D-80336 Munich, Germany.

PMID: 31296649
DOI: 10.1126/science.aaw9157

Abstract

The nuclear proteome is rich in stress-sensitive proteins, which suggests that effective protein quality control mechanisms are in place to ensure conformational maintenance. We investigated the role of the nucleolus in this process. In mammalian tissue culture cells under stress conditions, misfolded proteins entered the granular component (GC) phase of the nucleolus. Transient associations with nucleolar proteins such as NPM1 conferred low mobility to misfolded proteins within the liquid-like GC phase, avoiding irreversible aggregation. Refolding and extraction of proteins from the nucleolus during recovery from stress was Hsp70-dependent. The capacity of the nucleolus to store misfolded proteins was limited, and prolonged stress led to a transition of the nucleolar matrix from liquid-like to solid, with loss of reversibility and dysfunction in quality control. Thus, we suggest that the nucleolus has chaperone-like properties and can promote nuclear protein maintenance under stress.

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Comment in

Nucleolus: A Liquid Droplet Compartment for Misbehaving Proteins.
Alberti S, Carra S. Alberti S, et al. Curr Biol. 2019 Oct 7;29(19):R930-R932. doi: 10.1016/j.cub.2019.08.013. Curr Biol. 2019. PMID: 31593669
Nucleolus: A Protein Quality Control Compartment.
Rekulapally P, Suresh SN. Rekulapally P, et al. Trends Biochem Sci. 2019 Dec;44(12):993-995. doi: 10.1016/j.tibs.2019.10.001. Epub 2019 Oct 23. Trends Biochem Sci. 2019. PMID: 31668600

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The nucleolus functions as a phase-separated protein quality control compartment

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