Phospholemman: A Novel Cardiac Stress Protein

Authors: Cheung, Joseph Y.; Zhang, Xue-Qian; Song, Jianliang; Gao, Erhe; Rabinowitz, Joseph E.; Chan, Tung O.; Wang, JuFang

Source: Clinical and Translational Science, Volume 3, Number 4, August 2010 , pp. 189-196(8)

Publisher: Wiley-Blackwell

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Abstract:

Abstract

Phospholemman (PLM), a member of the FXYD family of regulators of ion transport, is a major sarcolemmal substrate for protein kinases A and C in cardiac and skeletal muscle. In the heart, PLM co-localizes and co-immunoprecipitates with Na+-K+-ATPase, Na+/Ca2+ exchanger, and L-type Ca2+ channel. Functionally, when phosphorylated at serine68, PLM stimulates Na+-K+-ATPase but inhibits Na+/Ca2+ exchanger in cardiac myocytes. In heterologous expression systems, PLM modulates the gating of cardiac L-type Ca2+ channel. Therefore, PLM occupies a key modulatory role in intracellular Na+ and Ca2+ homeostasis and is intimately involved in regulation of excitation–contraction (EC) coupling. Genetic ablation of PLM results in a slight increase in baseline cardiac contractility and prolongation of action potential duration. When hearts are subjected to catecholamine stress, PLM minimizes the risks of arrhythmogenesis by reducing Na+ overload and simultaneously preserves inotropy by inhibiting Na+/Ca2+ exchanger. In heart failure, both expression and phosphorylation state of PLM are altered and may partly account for abnormalities in EC coupling. The unique role of PLM in regulation of Na+-K+-ATPase, Na+/Ca2+ exchanger, and potentially L-type Ca2+ channel in the heart, together with the changes in its expression and phosphorylation in heart failure, make PLM a rational and novel target for development of drugs in our armamentarium against heart failure. Clin Trans Sci 2010; Volume 3: 189–196

Keywords: ion transport regulator; phospholemman; protein kinase

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1752-8062.2010.00213.x

Affiliations: Division of Nephrology and Center of Translational Medicine, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Publication date: August 1, 2010

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