Plasma Membrane Calcium ATPase
To function properly, cells must maintain a very low cytosolic free Ca2+ concentration (50–200 nM) in the face of an extracellular concentration, which is 1–2 mM, and can reach even 10 mM in sea water, which is the extracellular ambient of some cells, e.g
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Plasma Membrane Calcium ATPase
E. Carafoli . D. Lim
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Historical Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 582
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General Properties of the PMCA Pump . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 582
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Primary Structure of the PMCA Pump . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583
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Membrane Topology and Functional Domains of the PMCA Pump . . . . . . . . . . . . . . . . . . . . . . . . . . . 583
5 Isoforms of the PMCA Pump . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 584 5.1 Distribution of PMCA Isoforms in the Adult Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 584 5.2 Developmental Changes in the PMCA Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 585 6 Splicing Variants of the PMCA Pumps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 586 6.1 Functional Diversity of the PMCAs: Structure–Function Relationships . . . . . . . . . . . . . . . . . . . . . . . . . . 587 7
Regulation of the Activity of the PMCA Interaction with Modulators . . . . . . . . . . . . . . . . . . . . . . . . . 588
8 8.1 8.2 8.3
PMCA Pumps and Pathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 590 Studies on PMCA Knock-Out Mice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 590 PMCA2 Mutants and Hereditary Hearing Loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 590 PMCA Pumps in Other Pathological Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 591
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Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 592
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2009 Springer Science+Business Media, LLC.
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Plasma membrane calcium ATPase
Abstract: To function properly, cells must maintain a very low cytosolic free Ca2+ concentration (50–200 nM) in the face of an extracellular concentration, which is 1–2 mM, and can reach even 10 mM in sea water, which is the extracellular ambient of some cells, e.g., oocytes, of some marine species. To maintain such a steep concentration gradient, eukaryotic cells have developed efficient systems for Ca2+ extrusion. Two of them operate in the plasma membrane, a Ca2+ ATPase (PMCA pump), and a Na+/Ca2+ exchanger (NCX), two inside the cell, in the endo(sarco)plasmic reticulum (ER) (a Ca2+ ATPase, the SERCA pum
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