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.
Similar content being viewed by others
References
Schtazmann H. J. (1996) ATP-dependent Ca++ extrusion from human red cells. Experientia22: 364–368
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
Pedersen P. L. and Carafoli E. (1987) Ion motive ATPases I: ubiquity, properties and significance to cell function. Trends Biochem. Sci.12: 146–150
Pedersen P. L. and Carafoli E. (1987) Ion motive ATPases II: energy-coupling and work output. Trends Biochem. Sci.12: 186–189
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
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
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
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
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
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
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
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
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
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
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
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
Rega A. F. and Garrahan P. J. (1986) The Ca2+ pump of plasma membranes, CRC Press, Boca Raton
Carafoli E. (1991) The calcium pump of the plasma membrane. Physiol Rev.71: 129–153
Carafoli E. (1991) The calcium pump of the plasma membrane. J. Biol. Chem.267: 2115–2118
Carafoli E. (1994) Plasma membrane calcium ATPase: 15 years of work on the purified enzyme. FASEB J.8: 993–1007
Penniston J. T. and Enyedi A. (1994) Plasma membrane Ca2+ pump: recent developments. Cell Physiol. Biochem.4: 148–159
Monteith, G. R. and Roufogalis B. D. (1995) The plasma membrane calcium pump—a physiological perspective on its regulation. Cell Calcium18: 459–476
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
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
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
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
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
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
Machamer C. E. (1993) Targeting and retention of golgi membrane proteins. Curr. Opin. Cell Biol.5: 606–617
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
Carafoli E. and Guerini D. (1993) Molecular and cellular biology of plasma membrane Ca2+ ATPase. Trends in Cardiovasc. Med.3: 177–184
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
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
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
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
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
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
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
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
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
Author information
Authors and Affiliations
Rights 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
Issue Date:
DOI: https://doi.org/10.1007/BF01952107