Evidence map›Paper›PMID 33649309›Full record

ArticleNature communications2021

Cells recognize osmotic stress through liquid-liquid phase separation lubricated with poly(ADP-ribose).

Kengo Watanabe, Kazuhiro Morishita, Xiangyu Zhou, Shigeru Shiizaki, Yasuo Uchiyama, Masato Koike, Isao Naguro, Hidenori Ichijo

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
6.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

66 citing papers in PubMed, 115 citations in OpenAlex.

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  13. FLL2 modulatesiScience · 2025
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6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Kengo WatanabeLaboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan. kwatanabe@15.alumni.u-tokyo.ac.jp.ORCID 0000-0002-0348-1634
Kazuhiro MorishitaLaboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan.
Xiangyu ZhouLaboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan.
Shigeru ShiizakiLaboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan.
Yasuo UchiyamaDepartment of Cellular and Molecular Neuropathology, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan.
Masato KoikeDepartment of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan.ORCID 0000-0002-3174-5684
Isao NaguroLaboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan.ORCID 0000-0002-0338-8026
Hidenori IchijoLaboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan. ichijo@mol.f.u-tokyo.ac.jp.ORCID 0000-0002-5005-6438
The University of Tokyo · JPJuntendo University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cells are under threat of osmotic perturbation; cell volume maintenance is critical in cerebral edema, inflammation and aging, in which prominent changes in intracellular or extracellular osmolality emerge. After osmotic stress-enforced cell swelling or shrinkage, the cells regulate intracellular osmolality to recover their volume. However, the mechanisms recognizing osmotic stress remain obscured. We previously clarified that apoptosis signal-regulating kinase 3 (ASK3) bidirectionally responds to osmotic stress and regulates cell volume recovery. Here, we show that macromolecular crowding induces liquid-demixing condensates of ASK3 under hyperosmotic stress, which transduce osmosensing signal into ASK3 inactivation. A genome-wide small interfering RNA (siRNA) screen identifies an ASK3 inactivation regulator, nicotinamide phosphoribosyltransferase (NAMPT), related to poly(ADP-ribose) signaling. Furthermore, we clarify that poly(ADP-ribose) keeps ASK3 condensates in the liquid phase and enables ASK3 to become inactivated under hyperosmotic stress. Our findings demonstrate that cells rationally incorporate physicochemical phase separation into their osmosensing systems.

Indexed as

LubricationOsmotic PressureAmino Acid MotifsAmino Acid SequenceCytokinesHEK293 CellsHumansMAP Kinase Kinase KinasesModels, MolecularMutationNADNicotinamide PhosphoribosyltransferasePhosphoprotein PhosphatasesPoly Adenosine Diphosphate RiboseProtein DomainsCytokinesMAP3K15 protein, humanMAP Kinase Kinase KinasesNADNicotinamide Phosphoribosyltransferasenicotinamide phosphoribosyltransferase, humanPhosphoprotein PhosphatasesPoly Adenosine Diphosphate Riboseprotein phosphatase 6

Identifiers

PMID33649309
PMCPMC7921423
OpenAlexW3135686923

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.