The nucleolus functions as a phase-separated protein quality control compartment - PubMed (original) (raw)
. 2019 Jul 26;365(6451):342-347.
doi: 10.1126/science.aaw9157. Epub 2019 Jul 11.
Affiliations
- PMID: 31296649
- DOI: 10.1126/science.aaw9157
The nucleolus functions as a phase-separated protein quality control compartment
F Frottin et al. Science. 2019.
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.
Copyright © 2019, American Association for the Advancement of Science.
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
Similar articles
- The Nucleolus as a Proteostasis Regulator.
Amer-Sarsour F, Ashkenazi A. Amer-Sarsour F, et al. Trends Cell Biol. 2019 Nov;29(11):849-851. doi: 10.1016/j.tcb.2019.08.002. Epub 2019 Aug 28. Trends Cell Biol. 2019. PMID: 31473054 - Self-interaction of NPM1 modulates multiple mechanisms of liquid-liquid phase separation.
Mitrea DM, Cika JA, Stanley CB, Nourse A, Onuchic PL, Banerjee PR, Phillips AH, Park CG, Deniz AA, Kriwacki RW. Mitrea DM, et al. Nat Commun. 2018 Feb 26;9(1):842. doi: 10.1038/s41467-018-03255-3. Nat Commun. 2018. PMID: 29483575 Free PMC article. - Protein quality control in the nucleolus safeguards recovery of epigenetic regulators after heat shock.
Azkanaz M, Rodríguez López A, de Boer B, Huiting W, Angrand PO, Vellenga E, Kampinga HH, Bergink S, Martens JH, Schuringa JJ, van den Boom V. Azkanaz M, et al. Elife. 2019 Jun 14;8:e45205. doi: 10.7554/eLife.45205. Elife. 2019. PMID: 31199242 Free PMC article. - Spatially organized aggregation of misfolded proteins as cellular stress defense strategy.
Miller SB, Mogk A, Bukau B. Miller SB, et al. J Mol Biol. 2015 Apr 10;427(7):1564-74. doi: 10.1016/j.jmb.2015.02.006. Epub 2015 Feb 11. J Mol Biol. 2015. PMID: 25681695 Review.
Cited by
- Quality control of cytoplasmic proteins inside the nucleus.
Borgert L, Mishra S, den Brave F. Borgert L, et al. Comput Struct Biotechnol J. 2022 Aug 23;20:4618-4625. doi: 10.1016/j.csbj.2022.08.033. eCollection 2022. Comput Struct Biotechnol J. 2022. PMID: 36090811 Free PMC article. Review. - Altered Phase Separation and Cellular Impact in _C9orf72_-Linked ALS/FTD.
Solomon DA, Smikle R, Reid MJ, Mizielinska S. Solomon DA, et al. Front Cell Neurosci. 2021 Apr 21;15:664151. doi: 10.3389/fncel.2021.664151. eCollection 2021. Front Cell Neurosci. 2021. PMID: 33967699 Free PMC article. - PABP-driven secondary condensed phase within RSV inclusion bodies activates viral mRNAs for ribosomal recruitment.
Zhang Q, Ye H, Liu C, Zhou H, He M, Liang X, Zhou Y, Wang K, Qin Y, Li Z, Chen M. Zhang Q, et al. Virol Sin. 2024 Apr;39(2):235-250. doi: 10.1016/j.virs.2023.12.001. Epub 2023 Dec 9. Virol Sin. 2024. PMID: 38072230 Free PMC article. - Real-time imaging of RNA polymerase I activity in living human cells.
Fu Y, Liu Y, Wen T, Fang J, Chen Y, Zhou Z, Gu X, Wu H, Sheng J, Xu Z, Zou W, Chen B. Fu Y, et al. J Cell Biol. 2023 Jan 2;222(1):e202202110. doi: 10.1083/jcb.202202110. Epub 2022 Oct 25. J Cell Biol. 2023. PMID: 36282216 Free PMC article. - 3D genome, on repeat: Higher-order folding principles of the heterochromatinized repetitive genome.
Haws SA, Simandi Z, Barnett RJ, Phillips-Cremins JE. Haws SA, et al. Cell. 2022 Jul 21;185(15):2690-2707. doi: 10.1016/j.cell.2022.06.052. Cell. 2022. PMID: 35868274 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous