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The role of SERCA2a/PLN complex, Ca2+ homeostasis, and anti-apoptotic proteins in determining cell fate

  • Cardiovascular Physiology
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Intracellular calcium is a major coordinator of numerous aspects of cellular physiology, including muscle contractility and cell survival. In cardiac muscle, aberrant Ca2+ cycling has been implicated in a range of pathological conditions including cardiomyopathies and heart failure. The sarco(endo)plasmic reticulum Ca2+ transport adenosine triphosphatase (SERCA2a) and its regulator phospholamban (PLN) have a central role in modulating Ca2+ homeostasis and, therefore, cardiac function. Herein, we discuss the mechanisms through which SERCA2a and PLN control cardiomyocyte function in health and disease. Emphasis is placed on our newly identified PLN-binding partner HS-1-associated protein X-1 (HAX-1), which has an anti-apoptotic function and presents with numerous similarities to Bcl-2. Recent evidence indicates that proteins of the Bcl-2 family can influence ER Ca2+ content, a critical determinant of cellular sensitivity to apoptosis. The discovery of the PLN/HAX-1 interaction therefore unveils an important new link between Ca2+ homeostasis and cell survival, with significant therapeutic potential.

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Acknowledgment

This work was supported by research funds from the Biomedical Research Foundation, Academy of Athens; the John F. Kostopoulos Foundation; the Hellenic Cardiological Society; NIH HL26057, HL64018, and HL77101; the Leducq Foundation Trans-Antlantic alliance; and by the European Union Sixth Framework Program for Research and Technological Development, “Life Sciences, Genomics and Biotechnology for Health,” Valapodyn, contract #LSHG-CT-2006-037277.

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  1. Molecular Biology Division, Biomedical Research Foundation, Academy of Athens, Soranou Efesiou 4, Athens, 115 27, Greece

    Elizabeth Vafiadaki, Vasiliki Papalouka, Demetrios A. Arvanitis, Evangelia G. Kranias & Despina Sanoudou

  2. Department of Pharmacology and Cell Biophysics, College of Medicine, University of Cincinnati, Cincinnati, OH, USA

    Evangelia G. Kranias

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  1. Elizabeth Vafiadaki
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Correspondence to Despina Sanoudou.

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Vafiadaki, E., Papalouka, V., Arvanitis, D.A. et al. The role of SERCA2a/PLN complex, Ca2+ homeostasis, and anti-apoptotic proteins in determining cell fate. Pflugers Arch - Eur J Physiol 457, 687–700 (2009). https://doi.org/10.1007/s00424-008-0506-5

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