Phospholemman (FXYD1) associates with Na,K-ATPase and regulates its transport properties

Crambert, Gilles; Füzesi, Maria; Garty, Haim; Karlish, Steven J. D.; Geering, Käthi

doi:10.1073/pnas.182267299

Cited by 255 publications

(320 citation statements)

References 44 publications

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“…The ryanodine receptor 2 (RYR2) is responsible for calcium release from sarcoplasmic reticulum critical to EC-coupling [31]. Phospholemman has been shown to regulate contractility, [Ca 2+ ] transients and Na + /Ca 2+ exchange [32,33]. Calcineurin is a Ca 2+ /calmodulin-regulated serine/threonine protein phosphatase involved in the WNT pathway for cardiac development and multiple signaling pathways leading to cardiac hypertrophy [34,35].…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic profiling of the canine tachycardia-induced heart failure model: global comparison to human and murine heart failure

Zhong

DiSilvestre

et al. 2006

Journal of Molecular and Cellular Cardiology

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Alterations of cardiac gene expression are central to ventricular dysfunction in human heart failure (HF). The canine tachycardia pacing-induced HF model is known to reproduce the main hemodynamic, echocardiographic and electrophysiological changes observed in human HF. In this study, we use this HF model to compare gene expression profiles in the left and right ventricles (LV, RV) of normal and end-stage failing canine hearts and compare the transcription profiles to those in human and murine models of HF. In end-stage HF, the LV exhibits down regulation of genes involved in energy production, cardiac contraction, and modulation of excitation-contraction coupling as compared with normal LV. The majority of transcriptomic changes between normal and end-stage canine HF were shared by the RV and LV. Genes down regulated only in the LV included those involved in aerobic energy production pathways, regulation of actin filament length, and enzymelinked receptor protein signaling pathways. In normal canine hearts, genes encoding specific components of the contractile apparatus exhibit LV-RV asymmetric expression patterns; in failing hearts, cardiac fetal transcription factors MEF2 and MITF and the stress-responsive transcription factor ATF4 showed interventricular differences in expression. The comparison among the canine tachypacing, mouse transgenic, and human HF reveals that human disease involves down regulation of genes in a broad range of biological processes while experimentally induced HF is associated with down regulation of energy pathways, and that human ischemic HF and canine HF share a similar over representation of transcriptional pathways in the up regulated genes. This study provides insights into the molecular pathways leading to end-stage tachycardia-induced HF, and into global transcriptomic differences between the animal HF models and human HF.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic profiling of the canine tachycardia-induced heart failure model: global comparison to human and murine heart failure

Zhong

DiSilvestre

et al. 2006

Journal of Molecular and Cellular Cardiology

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“…FXYD2 or the ␥ subunit of Na,K-ATPase (8) was the first FXYD protein that was identified as a specific modulator of renal Na,K-ATPase (9 -13). It is now well established that also FXYD1 (phospholemman) (14), a phospholemman-like protein from shark (15), FXYD4 (corticosteroid hormone-induced factor) (11,16), and FXYD7 (17) also play a tissue-specific role in Na,K-ATPase regulation. Significantly, each of these auxiliary subunits produce a distinct functional effect on Na,K-ATPase that is adapted to the physiological needs of the tissues in which they are expressed.…”

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confidence: 99%

Structural and Functional Interaction Sites between Na,K-ATPase and FXYD Proteins

Grosdidier

Crambert

et al. 2004

Journal of Biological Chemistry

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Several members of the FXYD protein family are tissue-specific regulators of Na,K-ATPase that produce distinct effects on its apparent K ؉ and Na ؉ affinity. Little is known about the interaction sites between the Na,KATPase ␣ subunit and FXYD proteins that mediate the efficient association and/or the functional effects of FXYD proteins. In this study, we have analyzed the role of the transmembrane segment TM9 of the Na,K-ATPase ␣ subunit in the structural and functional interaction with FXYD2, FXYD4, and FXYD7. Mutational analysis combined with expression in Xenopus oocytes reveals that Phe 956 , Glu 960 , Leu 964 , and Phe 967 in TM9 of the Na,K-ATPase ␣ subunit represent one face interacting with the three FXYD proteins. Leu 964 and Phe 967 contribute to the efficient association of FXYD proteins with the Na,K-ATPase ␣ subunit, whereas Phe 956 and Glu 960 are essential for the transmission of the functional effect of FXYD proteins on the apparent K ؉ affinity of Na,K-ATPase. The relative contribution of Phe 956 and Glu 960 to the K ؉ effect differs for different FXYD proteins, probably reflecting the intrinsic differences of FXYD proteins on the apparent K ؉ affinity of Na,K-ATPase. In contrast to the effect on the apparent K ؉ affinity, Phe 956 and Glu 960 are not involved in the effect of FXYD2 and FXYD4 on the apparent Na ؉ affinity of Na,K-ATPase. The mutational analysis is in good agreement with a docking model of the Na,K-ATPase/ FXYD7 complex, which also predicts the importance of Phe 956 , Glu 960 , Leu 964 , and Phe 967 in subunit interaction. In conclusion, by using mutational analysis and modeling, we show that TM9 of the Na,K-ATPase ␣ subunit exposes one face of the helix that interacts with FXYD proteins and contributes to the stable interaction with FXYD proteins, as well as mediating the effect of FXYD proteins on the apparent K ؉ affinity of Na,K-ATPase.

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“…In this case, PKC-δ may directly phosphorylate the pump protein to induce conformational changes, thus decreasing the turnover rate of each pump [1,31] . In addition, the recent observation that phospholemman (FXYD1) associates with the cardiac Na + -K + pump [32] offers another subunit that may confer sensitivity to PKC-δ.…”

Section: Discussionmentioning

confidence: 99%

Isoform-specific regulation of the Na+-K+ pump by adenosine in guinea pig ventricular myocytes

et al. 2009

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Aim: The present study investigated the effect of adenosine on Na + -K + pumps in acutely isolated guinea pig (Cavia sp.) ventricular myocytes. Methods: The whole-cell, patch-clamp technique was used to record the Na + -K + pump current (I p ) in acutely isolated guinea pig ventricular myocytes. Results: Adenosine inhibited the high DHO-affinity pump current (I h ) in a concentration-dependent manner, which was blocked by the selective adenosine A 1 receptor antagonist DPCPX and the general protein kinase C (PKC) antagonists staurosporine, GF 109203X or the specific δ isoform antagonist rottlerin. In addition, the inhibitory action of adenosine was mimicked by a selective A 1 receptor agonist CCPA and a specific activator peptide of PKC-δ, PP114. In contrast, the selective A 2A receptor agonist CGS21680 and A 3 receptor agonist Cl-IB-MECA did not affect I h . Application of the selective A 2A receptor antagonist SCH58261 and A 3 receptor antagonist MRS1191 also failed to block the effect of adenosine. Furthermore, H89, a selective protein kinase A (PKA) antagonist, did not exert any effect on adenosine-induced I h inhibition. Conclusion:The present study provides the electrophysiological evidence that adenosine can induce significant inhibition of I h via adenosine A 1 receptors and the PKC-δ isoform.

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Phospholemman (FXYD1) associates with Na,K-ATPase and regulates its transport properties

Cited by 255 publications

References 44 publications

Transcriptomic profiling of the canine tachycardia-induced heart failure model: global comparison to human and murine heart failure

Transcriptomic profiling of the canine tachycardia-induced heart failure model: global comparison to human and murine heart failure

Structural and Functional Interaction Sites between Na,K-ATPase and FXYD Proteins

Isoform-specific regulation of the Na+-K+ pump by adenosine in guinea pig ventricular myocytes

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