Evidence map›Paper›PMID 34320358›Full record

ArticleCell reports2021

Molecular noise filtering in the β-adrenergic signaling network by phospholamban pentamers.

Daniel Koch, Alexander Alexandrovich, Florian Funk, Ay Lin Kho, Joachim P Schmitt, Mathias Gautel

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.3field-weighted citation impact, top 19% 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

6 citing papers in PubMed, 11 citations in OpenAlex.

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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

6 authors at 3 institutions in 2 countries.

Daniel KochRandall Centre for Cell and Molecular Biophysics, King's College London, SE1 1UL London, UK. Electronic address: dkoch.research@protonmail.com.
Alexander AlexandrovichRandall Centre for Cell and Molecular Biophysics, King's College London, SE1 1UL London, UK.
Florian FunkInstitute of Pharmacology and Clinical Pharmacology, and Cardiovascular Research Institute Düsseldorf (CARID), University Hospital Düsseldorf, 40225 Düsseldorf, Germany.
Ay Lin KhoRandall Centre for Cell and Molecular Biophysics, King's College London, SE1 1UL London, UK.
Joachim P SchmittInstitute of Pharmacology and Clinical Pharmacology, and Cardiovascular Research Institute Düsseldorf (CARID), University Hospital Düsseldorf, 40225 Düsseldorf, Germany.
Mathias GautelRandall Centre for Cell and Molecular Biophysics, King's College London, SE1 1UL London, UK.
King's College London · GBDüsseldorf University Hospital · DEHeinrich Heine University Düsseldorf · DE

Funding

British Heart Foundation CH/08/001/25300British Heart Foundation FS/17/65/33481Medical Research Council MR/R003106/1
6 · The paper itself

Abstract

Phospholamban (PLN) is an important regulator of cardiac calcium handling due to its ability to inhibit the calcium ATPase SERCA. β-Adrenergic stimulation reverses SERCA inhibition via PLN phosphorylation and facilitates fast calcium reuptake. PLN also forms pentamers whose physiological significance has remained elusive. Using mathematical modeling combined with biochemical and cell biological experiments, we show that pentamers regulate both the dynamics and steady-state levels of monomer phosphorylation. Substrate competition by pentamers and a feed-forward loop involving inhibitor-1 can delay monomer phosphorylation by protein kinase A (PKA), whereas cooperative pentamer dephosphorylation enables bistable PLN steady-state phosphorylation. Simulations show that phosphorylation delay and bistability act as complementary filters that reduce the effect of random fluctuations in PKA activity, thereby ensuring consistent monomer phosphorylation and SERCA activity despite noisy upstream signals. Preliminary analyses suggest that the PLN mutation R14del could impair noise filtering, offering a new perspective on how this mutation causes cardiac arrhythmias.

Indexed as

Protein MultimerizationSignal TransductionAnimalsBuffersCalcium-Binding ProteinsGene Regulatory NetworksHEK293 CellsHumansModels, BiologicalMutationPhospholambanPhosphorylationRatsRats, WistarReceptors, Adrenergic, betaBuffersCalcium-Binding ProteinsPhospholambanReceptors, Adrenergic, betabistabilitycalcium handlingcardiac arrhythmiascardiomyocyteshysteresisnon-linear dynamicsoligomerizationphosphorylationsignaling networkssystems biology

Identifiers

PMID34320358
PMCPMC8333238
OpenAlexW3186055267

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.