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PMID: 18415121 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

The role of SERCA2a/PLN complex, Ca(2+) homeostasis, and anti-apoptotic proteins in determining cell fate.

Pflugers Archiv : European journal of physiology ·Vol. 457 ·No. 3 ·2009-01-00 ·Pages 687-700

Vafiadaki E, Papalouka V, Arvanitis DA, Kranias EG, Sanoudou D

Abstract

Intracellular calcium is a major coordinator of numerous aspects of cellular physiology, including muscle contractility and cell survival. In cardiac muscle, aberrant Ca(2+) cycling has been implicated in a range of pathological conditions including cardiomyopathies and heart failure. The sarco(endo)plasmic reticulum Ca(2+) transport adenosine triphosphatase (SERCA2a) and its regulator phospholamban (PLN) have a central role in modulating Ca(2+) 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 Ca(2+) content, a critical determinant of cellular sensitivity to apoptosis. The discovery of the PLN/HAX-1 interaction therefore unveils an important new link between Ca(2+) homeostasis and cell survival, with significant therapeutic potential.

MeSH Terms
Adaptor Proteins, Signal Transducing Animals Animals, Genetically Modified Apoptosis Regulatory Proteins/metabolism Calcium/metabolism Calcium-Binding Proteins/metabolism Heart Failure/metabolism Homeostasis Humans Multiprotein Complexes/metabolism Myocytes, Cardiac/metabolism Proteins/metabolism Proto-Oncogene Proteins c-bcl-2/metabolism Sarcoplasmic Reticulum/metabolism Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism
Chemicals
Adaptor Proteins, Signal Transducing Apoptosis Regulatory Proteins Calcium-Binding Proteins HAX1 protein, human Multiprotein Complexes Proteins Proto-Oncogene Proteins c-bcl-2 phospholamban Sarcoplasmic Reticulum Calcium-Transporting ATPases Calcium
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Vafiadaki Elizabeth
Molecular Biology Division, Biomedical Research Foundation, Academy of Athens, Soranou Efesiou 4, Athens 115 27, Greece.
Papalouka Vasiliki
Arvanitis Demetrios A
Kranias Evangelia G
Sanoudou Despina
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Article Info
Journal
Pflugers Archiv : European journal of physiology
Abbr.
Pflugers Arch
ISSN
0031-6768
DOI
10.1007/s00424-008-0506-5
Published
2009-01-00
Epub
2008-00-16
Pages
687-700
Language
English
Region
Germany
NLM ID
0154720
Subset
IM
Grants
NHLBI NIH HHS · HL26057 · United States
NHLBI NIH HHS · HL64018 · United States
NHLBI NIH HHS · HL77101 · United States
External Links
PubMed source DOI: 10.1007/s00424-008-0506-5 View journal details
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