Borghi, Filipy;
Azevedo, Cristina;
Johnson, Errin;
Burden, Jemima J;
Saiardi, Adolfo;
(2024)
A mammalian model reveals inorganic polyphosphate channeling into the nucleolus and induction of a hyper-condensate state.
Cell Reports Methods
, 4
(7)
, Article 100814. 10.1016/j.crmeth.2024.100814.
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Abstract
Inorganic polyphosphate (polyP) is a ubiquitous polymer that controls fundamental processes. To overcome the absence of a genetically tractable mammalian model, we developed an inducible mammalian cell line expressing Escherichia coli polyphosphate kinase 1 (EcPPK1). Inducing EcPPK1 expression prompted polyP synthesis, enabling validation of polyP analytical methods. Virtually all newly synthesized polyP accumulates within the nucleus, mainly in the nucleolus. The channeled polyP within the nucleolus results in the redistribution of its markers, leading to altered rRNA processing. Ultrastructural analysis reveals electron-dense polyP structures associated with a hyper-condensed nucleolus resulting from an exacerbation of the liquid-liquid phase separation (LLPS) phenomena controlling this membraneless organelle. The selective accumulation of polyP in the nucleoli could be interpreted as an amplification of polyP channeling to where its physiological function takes place. Indeed, quantitative analysis of several mammalian cell lines confirms that endogenous polyP accumulates within the nucleolus.
| Type: | Article |
|---|---|
| Title: | A mammalian model reveals inorganic polyphosphate channeling into the nucleolus and induction of a hyper-condensate state |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.crmeth.2024.100814 |
| Publisher version: | https://doi.org/10.1016/j.crmeth.2024.100814 |
| Language: | English |
| Additional information: | © The Author(s), 2024. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ |
| Keywords: | inorganic polyphosphates, liquid-liquid phase separation, polyphosphorilation, nucleus, nucleolus, toluidine blue, PPK1 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10198201 |
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