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Nature and site of phospholamban regulation of the Ca2+ pump of sarcoplasmic reticulum

Nature volume 342, pages 90–92 (1989)Cite this article

Abstract

THE rapid removal of Ca2+ ions from the cytosol, necessary for the efficient relaxation of cardiac muscle cells, is performed by the Ca2+-pumping ATPase of the sarcoplasmic reticulum. The calcium pump is activated by cyclic AMP- and calmodulin-dependent phosphorylation of phospholamban, an integral membrane protein of the sarcoplasmic reticulum. Using a heterobifunctional crosslinking agent which can be cleaved and photoactivated, we provide evidence for a direct interaction between the two proteins. Only the non-phosphorylated form of phospholamban interacts with the ATPase, demonstrating that phospholamban is an endogenous inhibitor that is removed from the ATPase by phosphorylation. Non-phosphorylated phospholamban interacts only with the calcium-free conformation of the ATPase and is released when it is converted to the calcium-bound state. We localized the site of interaction to a single peptide isolated after cyanogen bromide cleavage of the ATPase. The peptide derives from a domain just C-terminal to the aspartyl phosphate of the active site. This domain is unique to ATPases of the sarcoplasmic reticulum in that it has no homology with any other phosphorylation-type ion pump. The domain occurs in both slow- and fast-twitch isoforms of the ATPase, even though phospholamban is not expressed in fast-twitch muscles.

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Author notes

  1. M. Inui and M. Tada: First Department of Medicine and Pathophysiology, Osaka University School of Medicine, Osaka 553, Japan

  2. M. Chiesi: Department of Cardiovascular Research, Pharmaceuticals Division, Ciba-Geigy Ltd, 4000 Basel, Switzerland

Authors and Affiliations

  1. Laboratory of Biochemistry, Swiss Federal Institute of Technology, 8092, Zürich, Switzerland

    P. James, M. Inui, M. Tada, M. Chiesi & E. Carafoli

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  1. P. James
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  2. M. Inui
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  3. M. Tada
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  4. M. Chiesi
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  5. E. Carafoli
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James, P., Inui, M., Tada, M. et al. Nature and site of phospholamban regulation of the Ca2+ pump of sarcoplasmic reticulum. Nature 342, 90–92 (1989). https://doi.org/10.1038/342090a0

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