Evidence map›Paper›PMID 26668322›Full record

ArticleThe Journal of biological chemistry2016

Protein Phosphatase 1c Associated with the Cardiac Sodium Calcium Exchanger 1 Regulates Its Activity by Dephosphorylating Serine 68-phosphorylated Phospholemman.

Tandekile Lubelwana Hafver, Kjetil Hodne, Pimthanya Wanichawan, Jan Magnus Aronsen, Bjørn Dalhus, Per Kristian Lunde, Marianne Lunde, Marita Martinsen, Ulla Helene Enger, William Fuller and 4 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

7 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. How does pressure overload cause cardiac hypertrophy and dysfunction? High-ouabain affinity cardiac NaAmerican journal of physiology. Heart and circulatory physiology · 2017
    Review
  5. Article
  6. Article
  7. Pivotal role of α2 NaThe Journal of physiology · 2016
    Review
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

14 authors at 4 institutions in 2 countries.

Tandekile Lubelwana HafverFrom the Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway, the KG Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, 0316 Oslo, Norway.
Kjetil HodneFrom the Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway, the KG Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, 0316 Oslo, Norway, the Department of Basic Sciences and Aquatic Medicine, Norwegian University of Life Sciences (NMBU), 0454 Oslo, Norway.
Pimthanya WanichawanFrom the Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway, the KG Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, 0316 Oslo, Norway.
Jan Magnus AronsenFrom the Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway, the Bjørknes College, Oslo, Norway.
Bjørn Dalhusthe Department of Microbiology, Oslo University Hospital, Rikshospitalet, 0424 Oslo, Norway, the Department of Medical Biochemistry, Institute for Clinical Medicine, University of Oslo, 0424 Oslo, Norway and.
Per Kristian LundeFrom the Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway, the KG Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, 0316 Oslo, Norway.
Marianne LundeFrom the Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway, the KG Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, 0316 Oslo, Norway.
Marita MartinsenFrom the Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway, the KG Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, 0316 Oslo, Norway.
Ulla Helene EngerFrom the Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway, the KG Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, 0316 Oslo, Norway.
William Fullerthe Cardiovascular and Diabetes Medicine, School of Medicine, University of Dundee, Dundee, Scotland, United Kingdom DD1 9SY.
Ivar SjaastadFrom the Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway, the KG Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, 0316 Oslo, Norway.
William Edward LouchFrom the Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway, the KG Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, 0316 Oslo, Norway.
Ole Mathias SejerstedFrom the Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway, the KG Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, 0316 Oslo, Norway.
Cathrine Rein CarlsonFrom the Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway, the KG Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, 0316 Oslo, Norway, c.r.carlson@medisin.uio.no.
Oslo University Hospital · NOInstitutt for Eksperimentell Medisinsk Forskning · NOUniversity of Oslo · NOUniversity of Dundee · GB

Funding

British Heart Foundation FS/13/22/30126British Heart Foundation PG/10/93/28650British Heart Foundation PG/12/6/29366
6 · The paper itself

Abstract

The sodium (Na(+))-calcium (Ca(2+)) exchanger 1 (NCX1) is an important regulator of intracellular Ca(2+) homeostasis. Serine 68-phosphorylated phospholemman (pSer-68-PLM) inhibits NCX1 activity. In the context of Na(+)/K(+)-ATPase (NKA) regulation, pSer-68-PLM is dephosphorylated by protein phosphatase 1 (PP1). PP1 also associates with NCX1; however, the molecular basis of this association is unknown. In this study, we aimed to analyze the mechanisms of PP1 targeting to the NCX1-pSer-68-PLM complex and hypothesized that a direct and functional NCX1-PP1 interaction is a prerequisite for pSer-68-PLM dephosphorylation. Using a variety of molecular techniques, we show that PP1 catalytic subunit (PP1c) co-localized, co-fractionated, and co-immunoprecipitated with NCX1 in rat cardiomyocytes, left ventricle lysates, and HEK293 cells. Bioinformatic analysis, immunoprecipitations, mutagenesis, pulldown experiments, and peptide arrays constrained PP1c anchoring to the K(I/V)FF motif in the first Ca(2+) binding domain (CBD) 1 in NCX1. This binding site is also partially in agreement with the extended PP1-binding motif K(V/I)FF-X5-8Φ1Φ2-X8-9-R. The cytosolic loop of NCX1, containing the K(I/V)FF motif, had no effect on PP1 activity in an in vitro assay. Dephosphorylation of pSer-68-PLM in HEK293 cells was not observed when NCX1 was absent, when the K(I/V)FF motif was mutated, or when the PLM- and PP1c-binding sites were separated (mimicking calpain cleavage of NCX1). Co-expression of PLM and NCX1 inhibited NCX1 current (both modes). Moreover, co-expression of PLM with NCX1(F407P) (mutated K(I/V)FF motif) resulted in the current being completely abolished. In conclusion, NCX1 is a substrate-specifying PP1c regulator protein, indirectly regulating NCX1 activity through pSer-68-PLM dephosphorylation.

Indexed as

Disease Models, AnimalProtein Processing, Post-TranslationalAnimalsAnimals, NewbornCells, CulturedComputational BiologyHeart FailureHEK293 CellsHumansMaleMembrane ProteinsMutant ProteinsMyocytes, CardiacPhosphoproteinsPhosphorylationProtein Interaction Domains and MotifsMembrane ProteinsMutant ProteinsphospholemmanPhosphoproteinsPpp1cc protein, ratProtein Phosphatase 1Recombinant ProteinsSerineSodium-Calcium Exchangersodium-calcium exchanger 1animal modelcomputer modelingelectrophysiologyheart failureion channelpeptide arrayphosphoprotein phosphatase 1 (PP1)protein motifprotein-protein interactionsodium-calcium exchange

Identifiers

PMID26668322
PMCPMC4813481
OpenAlexW2220766880

What OpenQuestion holds

Textmetadata
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.