Evidence map›Paper›PMID 30715853›Full record

ArticleACS nano2019

Three-Dimensional and Chemical Mapping of Intracellular Signaling Nanodomains in Health and Disease with Enhanced Expansion Microscopy.

Thomas M D Sheard, Miriam E Hurley, John Colyer, Ed White, Ruth Norman, Eleftheria Pervolaraki, Kaarjel K Narayanasamy, Yufeng Hou, Hannah M Kirton, Zhaokang Yang and 8 more

Open access · hybridAbstract read
In one paragraph

Article in ACS nano, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
7.7field-weighted citation impact, top 3% 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

31 citing papers in PubMed, 45 citations in OpenAlex.

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  12. CaJournal of molecular and cellular cardiology · 2023
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  16. Three-dimensional visualization of the cardiac ryanodine receptor clusters and the molecular-scale fraying of dyads.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022
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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

18 authors at 4 institutions in 3 countries.

Thomas M D SheardSchool of Biomedical Sciences, Faculty of Biological Sciences , University of Leeds , Leeds LS2 9JT , United Kingdom.
Miriam E HurleySchool of Biomedical Sciences, Faculty of Biological Sciences , University of Leeds , Leeds LS2 9JT , United Kingdom.
John ColyerSchool of Biomedical Sciences, Faculty of Biological Sciences , University of Leeds , Leeds LS2 9JT , United Kingdom.
Ed WhiteSchool of Biomedical Sciences, Faculty of Biological Sciences , University of Leeds , Leeds LS2 9JT , United Kingdom.
Ruth NormanSchool of Biomedical Sciences, Faculty of Biological Sciences , University of Leeds , Leeds LS2 9JT , United Kingdom.
Eleftheria PervolarakiSchool of Biomedical Sciences, Faculty of Biological Sciences , University of Leeds , Leeds LS2 9JT , United Kingdom.
Kaarjel K NarayanasamySchool of Biomedical Sciences, Faculty of Biological Sciences , University of Leeds , Leeds LS2 9JT , United Kingdom.
Yufeng HouInstitute of Experimental Medical Research , Oslo University Hospital Ullevål , Oslo 0407 , Norway.
Hannah M KirtonSchool of Biomedical Sciences, Faculty of Biological Sciences , University of Leeds , Leeds LS2 9JT , United Kingdom.
Zhaokang YangSchool of Biomedical Sciences, Faculty of Biological Sciences , University of Leeds , Leeds LS2 9JT , United Kingdom.
Liam HunterSchool of Physics and Astronomy, Faculty of Mathematics and Physical Sciences , University of Leeds , Leeds LS2 9JT , United Kingdom.
Jung-Uk ShimSchool of Physics and Astronomy, Faculty of Mathematics and Physical Sciences , University of Leeds , Leeds LS2 9JT , United Kingdom.
Alexander H ClowsleyLiving Systems Institute , University of Exeter , Devon EX4 4QL , United Kingdom.
Andrew J SmithSchool of Biomedical Sciences, Faculty of Biological Sciences , University of Leeds , Leeds LS2 9JT , United Kingdom.
David BaddeleyAuckland Bioengineering Institute , University of Auckland , UniServices House, Level, 6/70 Symonds St , Grafton, Auckland 1010 , New Zealand.
Christian SoellerLiving Systems Institute , University of Exeter , Devon EX4 4QL , United Kingdom.
Michael A ColmanSchool of Biomedical Sciences, Faculty of Biological Sciences , University of Leeds , Leeds LS2 9JT , United Kingdom.
Izzy JayasingheSchool of Biomedical Sciences, Faculty of Biological Sciences , University of Leeds , Leeds LS2 9JT , United Kingdom.ORCID 0000-0003-2461-478X
University of Leeds · GBUniversity of Exeter · GBOslo University Hospital · NOUniversity of Auckland · NZ

Funding

British Heart Foundation RG/16/6/32233Medical Research Council MR/M014967/1Medical Research Council MR/M014967/2Wellcome TrustWellcome Trust 207684/Z/17/Z
6 · The paper itself

Abstract

Nanodomains are intracellular foci which transduce signals between major cellular compartments. One of the most ubiquitous signal transducers, the ryanodine receptor (RyR) calcium channel, is tightly clustered within these nanodomains. Super-resolution microscopy has previously been used to visualize RyR clusters near the cell surface. A majority of nanodomains located deeper within cells have remained unresolved due to limited imaging depths and axial resolution of these modalities. A series of enhancements made to expansion microscopy allowed individual RyRs to be resolved within planar nanodomains at the cell periphery and the curved nanodomains located deeper within the interiors of cardiomyocytes. With a resolution of ∼ 15 nm, we localized both the position of RyRs and their individual phosphorylation for the residue Ser2808. With a three-dimensional imaging protocol, we observed disturbances to the RyR arrays in the nanometer scale which accompanied right-heart failure caused by pulmonary hypertension. The disease coincided with a distinct gradient of RyR hyperphosphorylation from the edge of the nanodomain toward the center, not seen in healthy cells. This spatial profile appeared to contrast distinctly from that sustained by the cells during acute, physiological hyperphosphorylation when they were stimulated with a β-adrenergic agonist. Simulations of RyR arrays based on the experimentally determined channel positions and phosphorylation signatures showed how the nanoscale dispersal of the RyRs during pathology diminishes its intrinsic likelihood to ignite a calcium signal. It also revealed that the natural topography of RyR phosphorylation could offset potential heterogeneity in nanodomain excitability which may arise from such RyR reorganization.

Indexed as

Signal TransductionAdrenergic beta-AgonistsCalciumCalcium ChannelsHumansMicroscopyNanostructuresPhosphorylationRyanodine Receptor Calcium Release ChannelAdrenergic beta-AgonistsCalciumCalcium ChannelsRyanodine Receptor Calcium Release Channelcomputational modeling of intracellular calciumexpansion microscopyryanodine receptorsignaling nanodomainssite-specific phosphorylation

Identifiers

PMID30715853
PMCPMC6396323
OpenAlexW2911723462

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.