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1 Division of Cardiovascular Medicine, University of Virginia Health Center, Charlottesville, Virginia, USA; Division of Cardiovascular Research Center, University of Virginia Health Center, Charlottesville, Virginia, USA
2 Massachusetts General Hospital, Boston, Massachusetts, USA
3 Division of Cardiovascular Medicine, University of Virginia Health Center, Charlottesville, Virginia, USA
4 Transgenic Biology, Penn State University, University Park, Pennsylvania, USA
5 Division of Cardiovascular Research Center, University of Virginia Health Center, Charlottesville, Virginia, USA; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA
6 Division of Cardiovascular Research Center, University of Virginia Health Center, Charlottesville, Virginia, USA; Department of Radiology, University of Virginia, Charlottesville, Virginia, USA; Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA
7 Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana, USA
8 Division of Cardiovascular Medicine, University of Virginia Health Center, Charlottesville, Virginia, USA; Division of Cardiovascular Research Center, University of Virginia Health Center, Charlottesville, Virginia, USA; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA
* To whom correspondence should be addressed. E-mail: alt8t{at}virginia.edu.
Phospholemman (FXYD1), a 72 amino acid transmembrane protein abundantly expressed in heart and skeletal muscle, is a major substrate for phosphorylation in the
cardiomyocyte sarcolemma. Biochemical, cellular, and electrophysiological studies have suggested a number of possible roles for this protein, including ion channel modulator, taurinerelease channel, Na+:Ca2+ exchanger modulator, and Na,K-ATPase-associated subunit. We have
generated a phospholemman-deficient mouse. The adult null mice exhibited increased cardiac mass, larger cardiomyocytes, and ejection fractions that were 9% higher by magnetic resonance imaging, compared to wild type animals. Notably, this occurred in the absence of hypertension. Total Na,K-ATPase activity was 50% lower in the phospholemman-deficient hearts. Expression
(per unit of membrane protein) of total Na,K-ATPase was only slightly diminished, but expression of the minor 
2 isoform, which has been specifically implicated in the control of contractility, was reduced by 60%. The absence of phospholemman thus results in a complex
response including a surprisingly large reduction in intrinsic Na,K-ATPase activity, changes in
Na, K-ATPase isoform expression, increase in ejection fraction, and increase in cardiac mass. We hypothesize that a primary effect of phospholemman is to modulate the Na,K-ATPase, and that its reduced activity initiates compensatory responses.
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 D. Pavlovic, W. Fuller, and M. J. Shattock The intracellular region of FXYD1 is sufficient to regulate cardiac Na/K ATPase FASEB J, May 1, 2007; 21(7): 1539 - 1546. [Abstract] [Full Text] [PDF]
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 V. Deng, V. Matagne, F. Banine, M. Frerking, P. Ohliger, S. Budden, J. Pevsner, G. A. Dissen, L. S. Sherman, and S. R. Ojeda FXYD1 is an MeCP2 target gene overexpressed in the brains of Rett syndrome patients and Mecp2-null mice Hum. Mol. Genet., March 15, 2007; 16(6): 640 - 650. [Abstract] [Full Text] [PDF]
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E. Arystarkhova, C. Donnet, A. Munoz-Matta, S. C. Specht, and K. J. Sweadner Multiplicity of expression of FXYD proteins in mammalian cells: dynamic exchange of phospholemman and {gamma}-subunit in response to stress Am J Physiol Cell Physiol, March 1, 2007; 292(3): C1179 - C1191. [Abstract] [Full Text] [PDF]
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 W. Fuller and M. J. Shattock Phospholemman and the Cardiac Sodium Pump: Protein Kinase C, Take a Bow Circ. Res., December 8, 2006; 99(12): 1290 - 1292. [Full Text] [PDF]
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F. Han, J. Bossuyt, S. Despa, A. L. Tucker, and D. M. Bers Phospholemman Phosphorylation Mediates the Protein Kinase C-Dependent Effects on Na+/K+ Pump Function in Cardiac Myocytes Circ. Res., December 8, 2006; 99(12): 1376 - 1383. [Abstract] [Full Text] [PDF]
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A. L. Tucker, J. Song, X.-Q. Zhang, J. Wang, B. A. Ahlers, L. L. Carl, J. P. Mounsey, J. R. Moorman, L. I. Rothblum, and J. Y. Cheung Altered contractility and [Ca2+]i homeostasis in phospholemman-deficient murine myocytes: role of Na+/Ca2+ exchange Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2199 - H2209. [Abstract] [Full Text] [PDF]
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Y. Lifshitz, M. Lindzen, H. Garty, and S. J. D. Karlish Functional Interactions of Phospholemman (PLM) (FXYD1) with Na+,K+-ATPase: PURIFICATION OF {alpha}1/beta1/PLM COMPLEXES EXPRESSED IN PICHIA PASTORIS J. Biol. Chem., June 9, 2006; 281(23): 15790 - 15799. [Abstract] [Full Text] [PDF]
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 K. Geering FXYD proteins: new regulators of Na-K-ATPase Am J Physiol Renal Physiol, February 1, 2006; 290(2): F241 - F250. [Abstract] [Full Text] [PDF]
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