Evidence map›Paper›PMID 28094777›Full record

ArticleScientific reports2017

High resolution structural evidence suggests the Sarcoplasmic Reticulum forms microdomains with Acidic Stores (lysosomes) in the heart.

Daniel Aston, Rebecca A Capel, Kerrie L Ford, Helen C Christian, Gary R Mirams, Eva A Rog-Zielinska, Peter Kohl, Antony Galione, Rebecca A B Burton, Derek A Terrar

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
4.4field-weighted citation impact, top 6% 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

54 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.

  1. The protein interaction networks of mucolipins and two-pore channels.Biochimica et biophysica acta. Molecular cell research · 2019
    Pooled it
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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

10 authors at 3 institutions in 2 countries.

Daniel AstonDepartment of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK; BHF Centre of Research Excellence, University of Oxford, UK.
Rebecca A CapelDepartment of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK; BHF Centre of Research Excellence, University of Oxford, UK.
Kerrie L FordDepartment of Physiology, Anatomy and Genetics, Sherrington Building, University of Oxford, Sherrington Road, Oxford, OX1 3PT, UK; BHF Centre of Research Excellence, University of Oxford, UK.
Helen C ChristianDepartment of Physiology, Anatomy and Genetics, Sherrington Building, University of Oxford, Sherrington Road, Oxford, OX1 3PT, UK; BHF Centre of Research Excellence, University of Oxford, UK.
Gary R MiramsComputational Biology, Department of Computer Science, Wolfson Building, University of Oxford, Oxford, OX1 3QD, UK.
Eva A Rog-ZielinskaNational Heart and Lung Institute, Imperial College London, London, UK.
Peter KohlNational Heart and Lung Institute, Imperial College London, London, UK.
Antony GalioneDepartment of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK; BHF Centre of Research Excellence, University of Oxford, UK.
Rebecca A B BurtonDepartment of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK; BHF Centre of Research Excellence, University of Oxford, UK.
Derek A TerrarDepartment of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK; BHF Centre of Research Excellence, University of Oxford, UK.
University of Oxford · GBImperial College London · GBUniversitäts-Herzzentrum Freiburg-Bad Krozingen · DE

Funding

A MULTI-SCALE APPROACH TO CELL STRUCTURE & FUNCTIONP41GM103431 · NIGMS · UNIVERSITY OF COLORADO · PI HOENGER, ANDREAS · 2012 to 2014
$3.1M
British Heart Foundation FS/12/17/29532British Heart Foundation FS/15/3/31047British Heart Foundation RE/08/004NIGMS NIH HHS P41 GM103431Wellcome Trust 109371/Z/15/Z
6 · The paper itself

Abstract

Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) stimulates calcium release from acidic stores such as lysosomes and is a highly potent calcium-mobilising second messenger. NAADP plays an important role in calcium signalling in the heart under basal conditions and following β-adrenergic stress. Nevertheless, the spatial interaction of acidic stores with other parts of the calcium signalling apparatus in cardiac myocytes is unknown. We present evidence that lysosomes are intimately associated with the sarcoplasmic reticulum (SR) in ventricular myocytes; a median separation of 20 nm in 2D electron microscopy and 3.3 nm in 3D electron tomography indicates a genuine signalling microdomain between these organelles. Fourier analysis of immunolabelled lysosomes suggests a sarcomeric pattern (dominant wavelength 1.80 μm). Furthermore, we show that lysosomes form close associations with mitochondria (median separation 6.2 nm in 3D studies) which may provide a basis for the recently-discovered role of NAADP in reperfusion-induced cell death. The trigger hypothesis for NAADP action proposes that calcium release from acidic stores subsequently acts to enhance calcium release from the SR. This work provides structural evidence in cardiac myocytes to indicate the formation of microdomains between acidic and SR calcium stores, supporting emerging interpretations of NAADP physiology and pharmacology in heart.

Indexed as

AnimalsBiomarkersCalciumCalcium ChannelsCalcium SignalingHeart VentriclesLysosomal-Associated Membrane Protein 2LysosomesMaleMyocytes, CardiacNADPOrganellesRabbitsSarcoplasmic ReticulumBiomarkersCalciumCalcium ChannelsLysosomal-Associated Membrane Protein 2NAADPNADP

Identifiers

PMID28094777
PMCPMC5240626
OpenAlexW2579885605

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.