Skip to main content
Log in

The plasma membrane calcium pump: Recent developments and future perspectives

  • Milti-Author Reviews
  • Published:
Experientia Aims and scope Submit manuscript

Abstract

The Ca2+ pump of the plasma membrane (PMCA) is regulated by a number of agents. The most important is calmodulin (CaM), which binds to a domain located in the C-terminal portion of the pump, removing it from an autoinhibitory site next to the active site. The CaM-binding domain is preceded by an acidic sequence which contains a hidden signal for endoplasmic reticulum (ER) retention. Chimeras of the PMCA and endoplasmic reticulum (SERCA) pumps have revealed the presence of a strong signal for ER retention in the first 45 residues of the SERCA pump. Four gene products of the PMCA pump are known: two of them (1 and 4) are ubiquitously expressed, two (2 and 3) are specific for nerve cells and may be induced by their activation. Mutagenesis work has identified four residues in three of the transmembrane domains of the pump which may be components of the trans-protein Ca2+ path. The mutation of two of these residues alters the membrane targeting of the pump.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Schtazmann H. J. (1996) ATP-dependent Ca++ extrusion from human red cells. Experientia22: 364–368

    Article  Google Scholar 

  2. Cunningham K. W. and Fink G. R. (1994) Calcineurin-dependent growth control onSaccharomyces cerevisiae mutants lacking PMC1, a homologue of plasma membrane Ca2+ ATPases. J. Cell Biol.124: 351–362

    PubMed  Google Scholar 

  3. Pedersen P. L. and Carafoli E. (1987) Ion motive ATPases I: ubiquity, properties and significance to cell function. Trends Biochem. Sci.12: 146–150

    Article  Google Scholar 

  4. Pedersen P. L. and Carafoli E. (1987) Ion motive ATPases II: energy-coupling and work output. Trends Biochem. Sci.12: 186–189

    Article  Google Scholar 

  5. Gopinath R. M. and Vincenzi F. (1977) Phosphodiesterase protein activator mimics red blood cell cytoplasmatic activator of the (Ca2++Mg2+) ATPase. Biochem. Biophys. Res. Commun.77: 1203–1209

    PubMed  Google Scholar 

  6. Jarrett H. W. and Penniston J. T. (1977) Partial purification of the (Ca2++Mg2+)-ATPase activator from human erythrocytes: its similarity to the activator of 3′–5′ cyclic nucleotide phosphodiesterase. Biochem. Biophys. Res. Commun.77: 1210–1216

    PubMed  Google Scholar 

  7. Ronner P., Gazzotti P. and Carafoli E. (1977) A lipid requirement for the (Ca2++Mg2+)-activated ATPase of erythrocyte membranes. Arch. Biochem. Biophys.179: 578–583

    Article  PubMed  Google Scholar 

  8. Niggli V., Adunyah E. S. and Carafoli E. (1981) Acidic phospholipids, unsaturated fatty acids and limited proteolysis mimic the effect of calmodulin on the purified erythrocyte Ca2+-ATPase. J. Biol. Chem.256: 8588–8592

    PubMed  Google Scholar 

  9. Enyedi A., Sarkadi B., Szasz I., Bot B. and Gardos G. (1980) Molecular properties of the red cell calcium pump. II. Effects of proteolysis, proteolytic digestion and drugs on the calcium-induced phosphorylation by ATP in inside/out red cell membrane vesicles. Cell Calcium1: 299–310

    Article  Google Scholar 

  10. Caroni P. and Carafoli E. (1981) Regulation of Ca2+ pumping ATPase of heart sarcolemma by a phosphorylation/dephosphorylation process. J. Biol. Chem.256: 9371–9373

    Google Scholar 

  11. Wright L. C., Chen S. and Roufogalis B. D. (1993) Regulation of the activity and phosphorylation of the plasma membrane Ca2+-ATPase by protein kinase C in intact human erythrocytes. Arch. Biochem. Biophys.306: 277–284

    Article  PubMed  Google Scholar 

  12. Furukawa K. I., Tawada Y. and Shigekawa M. (1989) Protein kinase C activation stimulates plasma membane Ca2+ pump in cultured vascular smooth muscle cells. J. Biol. Chem.264: 4844–4849

    PubMed  Google Scholar 

  13. Kosk-Kosicka D. and Bzdega T. (1988) Activation of the erythrocyte Ca2+-ATPase by either self-association or interaction with calmodulin. J. Biol. Chem.263: 22–27

    Google Scholar 

  14. Niggli V., Adunyah E. S., Penniston J. T., and Carafoli E. (1981) Purified (Ca2++Mg2+)-ATPase of the erythrocyte membrane: reconstitution and effect of calmodulin and phospholipids. J. Biol. Chem.256: 395–401

    PubMed  Google Scholar 

  15. Niggli V., Adunyah E. S., Penniston, J. T., and Carafoli E. (1981) Purification of the (Ca2++Mg2+)-ATPase from human erythrocyte membranes using a calmodulin affinity column. J. Biol. Chem.254: 9955–9958

    Google Scholar 

  16. Schatzmann H. J. (1982) The calcium pump of erythrocytes and other animal cells. In: Membrane Transport of Calcium, pp. 41–108, Carafoli E. (ed.), Academic Press, London

    Google Scholar 

  17. Rega A. F. and Garrahan P. J. (1986) The Ca2+ pump of plasma membranes, CRC Press, Boca Raton

    Google Scholar 

  18. Carafoli E. (1991) The calcium pump of the plasma membrane. Physiol Rev.71: 129–153

    PubMed  Google Scholar 

  19. Carafoli E. (1991) The calcium pump of the plasma membrane. J. Biol. Chem.267: 2115–2118

    Google Scholar 

  20. Carafoli E. (1994) Plasma membrane calcium ATPase: 15 years of work on the purified enzyme. FASEB J.8: 993–1007

    PubMed  Google Scholar 

  21. Penniston J. T. and Enyedi A. (1994) Plasma membrane Ca2+ pump: recent developments. Cell Physiol. Biochem.4: 148–159

    Google Scholar 

  22. Monteith, G. R. and Roufogalis B. D. (1995) The plasma membrane calcium pump—a physiological perspective on its regulation. Cell Calcium18: 459–476

    Article  PubMed  Google Scholar 

  23. Hofmann F., James P., Vorherr T. and Carafoli E. (1993) The C-terminal domain of the plasma membrane Ca2+ pump contains 3 high affinity Ca2+ binding sites. J. Biol. Chem.268: 10252–10259

    PubMed  Google Scholar 

  24. Brodin P., Falchetto R., Vorherr T. and Carafoli E. (1992) Identification of two domains which mediate the binding of activating phospholipids to the plasma membrane Ca2+ pump. Eur. J. Biochem.204: 939–946

    Article  PubMed  Google Scholar 

  25. Falchetto R., Vorherr T., Brunner J. and Carafoli E. (1991) The plasma membrane Ca2+ pump contains a site that interact with its calmodulin-binding domain. J. Biol. Chem.266: 2930–2936

    PubMed  Google Scholar 

  26. Falchetto R., Vorherr T., Carafoli E. (1992) The calmodulin-binding site of the plasma membrane Ca2+ pump interacts with the transduction domain of the enzyme. Protein. Sci.1: 1613–1621

    PubMed  Google Scholar 

  27. James P., Vorherr T., Krebs, J., Morelli A., Castello G., McCormick D. J. et al. (1989) Modulation of erythrocyte Ca2+ ATPase by selective calpain cleavage of the calmodulin binding domain. J. Biol. Chem.264: 8289–8296

    PubMed  Google Scholar 

  28. Zvaritch E., Vellani F., Guerini D. and Carafoli E. (1995) A signal for endoplasmic reticulum retention located at the carboxyl terminus of the plasma membrane Ca2+-ATPase isoform 4Cl. J. Biol. Chem.270: 2679–2688

    Article  PubMed  Google Scholar 

  29. Machamer C. E. (1993) Targeting and retention of golgi membrane proteins. Curr. Opin. Cell Biol.5: 606–617

    Article  PubMed  Google Scholar 

  30. Foletti D., Guerini D. and Carafoli E. (1995) Subcellular targeting of the endoplasmic reticulum and plasma membrane Ca2+ pumps: a study using recombinant chimeras. FASEB J.9: 670–680

    PubMed  Google Scholar 

  31. Carafoli E. and Guerini D. (1993) Molecular and cellular biology of plasma membrane Ca2+ ATPase. Trends in Cardiovasc. Med.3: 177–184

    Article  Google Scholar 

  32. Heim R., Iwata T., Zvaritch E., Adamo H. P., Rütishauser B., Strehler E. E. et al. (1992) Expression, purification and properties of the plasma membrane Ca2+ pump and of its N-terminally truncated 105-kDa fragment. J. Biol. Chem.267: 24476–24484

    PubMed  Google Scholar 

  33. Hilfiker H., Guerini D. and Carafoli E. (1994) Cloning and expression of isoform 2 of the human plasma membrane Ca2+ ATPase. J. Biol Chem.268: 19717–19725

    Google Scholar 

  34. Stauffer T. P., Hilfiker H., Carafoli E. and Strehler E. E. (1993) Quantitative analysis of alternative splicing options for human plasma membrane calcium pump genes. J. Biol. Chem.268: 25993–26003

    PubMed  Google Scholar 

  35. Balàs R., Gallo R. and Kingsbury A. (1988) Effect of depolarisation on the maturation of cerebellar granule cells in culture. Dev. Brain Res.40: 269–276

    Article  Google Scholar 

  36. Gallo V., Kingsbury A., Balàs R. and Jørgensen O. S. (1987) The role of depolarization in the survival and differentiation of cerebellar granule cells in culture. J. Neurosci.7: 2203–2213

    PubMed  Google Scholar 

  37. Keeton T. P., Burk S. E. and Shull G. E. (1993) Alternative splicing of exons encoding the calmodulin-binding domains and C-termini of plasma membrane Ca2+-ATPase isoforms 1, 2, 3 and 4. J. Biol. Chem.268: 2740–2748

    PubMed  Google Scholar 

  38. Stauffer T., Guerini D. and Carafoli E. (1995) Tissue distribution of the four gene products of the plasma membrane Ca2+ pump. J. Biol. Chem.270: 12184–12190

    Article  PubMed  Google Scholar 

  39. Clarke D. M., Loo T. W., Inesi G. and MacLennan D. H. (1989) Location of the affinity Ca2+-binding sites within the predicted transmembrane domain of the sarcoplasmic reticulum Ca2+-ATPase. Nature239: 476–478

    Article  Google Scholar 

  40. Guerini D., Foletti D., Vellani F. and Carafoli E. (1996) Mutation of conserved residues in transmembrane domains 4, 6 and 8 causes loss of Ca2+ transport by the plasma membrane Ca2+ pump. Biochemistry35: 3290–3296

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carafoli, E., Garcia-Martin, E. & Guerini, D. The plasma membrane calcium pump: Recent developments and future perspectives. Experientia 52, 1091–1100 (1996). https://doi.org/10.1007/BF01952107

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01952107

Key words

Navigation