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The Plasma Membrane Calcium ATPase: Historical Appraisal and Some New Concepts

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Regulation of Ca2+-ATPases,V-ATPases and F-ATPases

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 14))

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Abstract

The plasma membrane calcium ATPase (PMCA pump) was discovered nearly 50 years ago. Among its functional properties, the wealth of regulatory mechanisms singles it out from all other members of the P-type ion pumps superfamily. The cytosolic C-terminal tail of the protein contains a binding domain for calmodulin, which binds to sites near the active site and maintains the enzyme autoinhibited in the resting state. Calmodulin removes the C-terminal domain from these docking sites, relieving the inhibition. Other pump regulators are the acidic phospholipids of the inner leaflet of the membrane, which are in principle sufficient for 50 % of maximal pump activity. The activation by acidic phospholipids could perhaps also be involved in the process of apoptosis, which is known to transfer the activatory phosphatidylserine to the outer leaflet of the membrane bilayer: the decreased Ca2+ ejection activity of the pump could amplify the cytosolic Ca2+ overload frequently involved in apoptosis. Another novel concept on the PMCA pump is the conclusion that its Ca2+ ejection activity is less important to the total regulation of cytosolic Ca2+ than that of the SERCA pump and the plasma membrane Na/Ca exchanger. The main role of the PMCA pump is instead the regulation of Ca2+ in restricted cytosolic domains in which it interacts with numerous important enzymes. The local regulation of Ca2+ necessarily confers to the activation by calmodulin an oscillatory character: as Ca2+ decreases in the local pump environment, calmodulin will leave the pump, terminating its activation.

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Authors and Affiliations

  1. Venetian Institute of Molecular Medicine, University of Padova, Via Orus, 2, 35129, Padova, Italy

    Ernesto Carafoli

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  1. Ernesto Carafoli
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Correspondence to Ernesto Carafoli .

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Editors and Affiliations

  1. Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. University of Manitoba, Institute of Cardiovascular Science St. Boniface Hospital Research, Winnipeg, Manitoba, Canada

    Naranjan S Dhalla

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Carafoli, E. (2016). The Plasma Membrane Calcium ATPase: Historical Appraisal and Some New Concepts. In: Chakraborti, S., Dhalla, N. (eds) Regulation of Ca2+-ATPases,V-ATPases and F-ATPases. Advances in Biochemistry in Health and Disease, vol 14. Springer, Cham. https://doi.org/10.1007/978-3-319-24780-9_1

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