Evidence map›Paper›PMID 20427316›Full record

ArticleJournal of cell science2010

Dynamic, inter-subunit interactions between the N-terminal and central mutation regions of cardiac ryanodine receptor.

Zheng Liu, Ruiwu Wang, Xixi Tian, Xiaowei Zhong, Jaya Gangopadhyay, Richard Cole, Noriaki Ikemoto, S R Wayne Chen, Terence Wagenknecht

Abstract read
In one paragraph

Article in Journal of cell science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.8field-weighted citation impact, top 5% 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

24 citing papers in PubMed, 41 citations in OpenAlex.

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  11. Integrins protect cardiomyocytes from ischemia/reperfusion injury.The Journal of clinical investigation · 2013
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Ryanodine receptors: structure and function.The Journal of biological chemistry · 2012
    Review
  19. Article
  20. Article
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

9 authors at 3 institutions in 2 countries.

Zheng LiuWadsworth Center, New York State Department of Health, Albany, NY 12201, USA. liuz@wadsworth.org
Ruiwu Wang
Xixi Tian
Xiaowei Zhong
Jaya Gangopadhyay
Richard Cole
Noriaki Ikemoto
S R Wayne Chen
Terence Wagenknecht
University of Calgary · CANew York State Department of Health · USBoston Biomedical Research Institute · US

Funding

ZERNIKE PHASE-CONTRAST IMAGINGP41RR001219 · NCRR · WADSWORTH CENTER · PI RENKEN, CHRISTIAN · 1985 to 2010
$11.1M
STRUCTURE OF CHANNELS IN EXCITATION/CONTRACTION COUPLINGR01AR040615 · NIAMS · WADSWORTH CENTER · PI WAGENKNECHT, TERENCE C · 1991 to 2014
$5.6M
Regulation of Normal and Diseased Cardiac Ca2+ ChannelsR01HL072841 · NHLBI · BOSTON BIOMEDICAL RESEARCH INSTITUTE · PI IKEMOTO, NORIAKI · 2003 to 2011
$3.5M
Structural Basis of Dysfunctional Calcium Release Channels in Heart DiseaseR01HL095541 · NHLBI · WADSWORTH CENTER · PI LIU, ZHENG · 2010 to 2013
$1.5M
CIHRNCRR NIH HHS P41 RR001219NCRR NIH HHS P41RR01219NHLBI NIH HHS R01 HL072841NHLBI NIH HHS R01HL072841NHLBI NIH HHS R01 HL095541NHLBI NIH HHS R01HL095541NIAMS NIH HHS R01 AR040615NIAMS NIH HHS R01AR040615
6 · The paper itself

Abstract

Naturally occurring mutations in the cardiac ryanodine receptor (RyR2) have been linked to certain types of cardiac arrhythmias and sudden death. Two mutation hotspots that lie in the N-terminal and central regions of RyR2 are predicted to interact with one another and to form an important channel regulator switch. To monitor the conformational dynamics involving these regions, we generated a fluorescence resonance energy transfer (FRET) pair. A yellow fluorescent protein (YFP) was inserted into RyR2 after residue Ser437 in the N-terminal region, and a cyan fluorescent protein (CFP) was inserted after residue Ser2367 in the central region, to form a dual YFP- and CFP-labeled RyR2 (RyR2(S437-YFP/S2367-CFP)). We transfected HEK293 cells with RyR2(S437-YFP/S2367-CFP) cDNAs, and then examined them by using confocal microscopy and by measuring the FRET signal in live cells. The FRET signals are influenced by modulators of RyR2, by domain peptides that mimic the effects of disease causing RyR2 mutations, and by various drugs. Importantly, FRET signals were also readily detected in cells co-transfected with single CFP (RyR2(S437-YFP)) and single YFP (RyR2(S2367-CFP)) labeled RyR2, indicating that the interaction between the N-terminal and central mutation regions is an inter-subunit interaction. Our studies demonstrate that FRET analyses of this CFP- and YFP-labeled RyR2 can be used not only for investigating the conformational dynamics associated with RyR2 channel gating, but potentially, also for identifying drugs that are capable of stabilizing the conformations of RyR2.

Indexed as

Arrhythmias, CardiacCalcium ChannelsCell LineCloning, MolecularDeath, Sudden, CardiacFluorescence Resonance Energy TransferGenetic Predisposition to DiseaseHumansMicroscopy, ConfocalModels, BiologicalMutationMyocardiumPolymorphism, GeneticProtein ConformationProtein Interaction Domains and MotifsRyanodine Receptor Calcium Release ChannelCalcium ChannelsRyanodine Receptor Calcium Release Channel

Identifiers

PMID20427316
PMCPMC2864716
OpenAlexW1974197507

What OpenQuestion holds

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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.