The Plasma Membrane Calcium Pump (PMCA): Regulation of Cytosolic Ca2+, Genetic Diversities and Its Role in Sub-plasma Membrane Microdomains

  • Joachim Krebs
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 981)


In this chapter the four different genes of the mammalian plasma membrane calcium ATPase (PMCA) and their spliced isoforms are discussed with respect to the structural and functional properties of PMCA, the tissue distribution of the different isoforms, including their differences during development. The importance of PMCA for regulating Ca2+ signaling in microdomains under different conditions is also discussed.


PMCA Ca2+ signaling Calcium homeostasis Second messenger Ca2+ microdomains CaMKIV Alternative splicing 



Thanks are due to Marek Michalak for critically reading the manuscript.

Conflict of Interest

The author declares no conflict of interests.


  1. 1.
    Krebs J (1995) Calcium, biochemistry. In: Meyers RA (ed) Encyclopedia of molecular biology and molecular medicine, vol 1. VCH, Weinheim, pp 237–250Google Scholar
  2. 2.
    Carafoli E, Krebs J (2016) Why calcium? How calcium became the best communicator. J Biol Chem 291:20849–20857CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Krebs J, Michalak M (2007) Calcium: a matter of life or death. Elsevier, AmsterdamGoogle Scholar
  4. 4.
    Kawasaki H, Nakayama S, Kretsinger RH (1998) Classification and evolution of EF-hand proteins. Biometals 11:277–295CrossRefPubMedGoogle Scholar
  5. 5.
    Kretsinger RH (1975) Hypothesis: calcium modulated proteins contain EF hands. In: Carafoli E, Clementi F, Drabikowski W, Margreth A (eds) Calcium transport in contraction and secretion. Elsevier, Amsterdam, pp 469–478Google Scholar
  6. 6.
    Kretsinger RH, Nockolds CE (1973) Carp muscle calcium-binding protein. II. Structure determination and general description. J Biol Chem 248:3313–3326PubMedGoogle Scholar
  7. 7.
    Efremov RG, Leitner A, Aebersold R, Raunser S (2015) Architecture and conformational switch mechanism of the ryanodine receptor. Nature 517:39–43CrossRefPubMedGoogle Scholar
  8. 8.
    Yan Z et al (2015) Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution. Nature 517:50–55CrossRefPubMedGoogle Scholar
  9. 9.
    Zalk R et al (2015) Structure of a mammalian ryanodine receptor. Nature 517:44–49CrossRefPubMedGoogle Scholar
  10. 10.
    Baughman JM et al (2011) Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 476:341–345CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    De Stefani D, Raffaello A, Teardo E, Szabo I, Rizzuto R (2011) A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 476:336–340CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Perocchi F et al (2010) MICU1 encodes a mitochondrial EF hand protein required for Ca(2+) uptake. Nature 467:291–296CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Caride AJ, Filoteo AG, Penniston JT, Strehler EE (2007) The plasma membrane Ca2+ pump isoform 4a differs from isoform 4b in the mechanism of calmodulin binding and activation kinetics. Implications for Ca2+ signaling. J Biol Chem 282:25640–25648CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Brini M, Carafoli E, Cali T (2017) The plasma membrane calcium pumps: focus on the role in (neuro) pathology. Biochem Biophys Res Commun 483:1116–1124CrossRefPubMedGoogle Scholar
  15. 15.
    Lopreiato R, Giacomello M, Carafoli E (2014) The plasma membrane calcium pump: new ways to look at an old enzyme. J Biol Chem 289:10261–10268CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Strehler EE (2015) Plasma membrane calcium ATPases: from generic Ca2+ sump pumps to versatile systems for fine- tuning cellular Ca2+. Biochem Biophys Res Commun 460:26–33CrossRefPubMedGoogle Scholar
  17. 17.
    Dunham ET, Glynn IM (1961) Adenosine triphosphatase activity and the active movements of alkali metal ions. J Physiol Lond 156:274–293CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Schatzmann HJ (1966) ATP-dependent Ca2+ extrusion from human red cells. Experientia 22:364–368CrossRefPubMedGoogle Scholar
  19. 19.
    Pederson PL, Carafoli E (1987) Ion motive ATPases. I. Ubiquity, properties, and significance for cell function. Trends Biochem Sci 12:146–150CrossRefGoogle Scholar
  20. 20.
    Pederson PL, Carafoli E (1987) Ion motive ATPases. II. Energy coupling and work output. Trends Biochem Sci 12:186–189CrossRefGoogle Scholar
  21. 21.
    Palmgren MG, Nissen P (2011) P-type ATPases. Annu Rev Biophys 40:243–266CrossRefPubMedGoogle Scholar
  22. 22.
    Gopinath RM, Vincenzi FF (1977) Phosphodiesterase protein activator mimics red blood cell cytoplasmic activator of the (Ca2+ + Mg2+) ATPase. Biochem Biophys Res Commun 77:1203–1209CrossRefPubMedGoogle Scholar
  23. 23.
    Jarrett HW, Penniston JT (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 77:1210–1216CrossRefPubMedGoogle Scholar
  24. 24.
    Niggli V, Penniston JT, Carafoli E (1979) Purification of the (Ca2+-Mg2+)-ATPase from human erythrocytes using a calmodulin affinity column. J Biol Chem 254:9955–9958PubMedGoogle Scholar
  25. 25.
    Niggli V, Adunyah ES, Penniston JT, Carafoli E (1981) Purified (Ca2+-Mg2+)-ATPase of the erythrocyte membrane. Reconstitution and effect of calmodulin and phospholipids. J Biol Chem 256:395–401PubMedGoogle Scholar
  26. 26.
    James P, Maeda M, Fischer R, Verma AK, Krebs J, Penniston JT, Carafoli E (1988) Identification and primary structure of a calmodulin binding domain of the Ca2+ pump of human erythrocytes. J Biol Chem 263:2905–2910PubMedGoogle Scholar
  27. 27.
    Shull GE, Greeb J (1988) Molecular cloning of two isoforms of the plasma membrane Ca2+-transporting ATPase from rat brain. Structural and functional domains exhibit similarity to Na+, K+− and other cation transport ATPases. J Biol Chem 263:8646–8657PubMedGoogle Scholar
  28. 28.
    Verma AK et al (1988) Complete primary structure of a human plasma membrane Ca2+ pump. J Biol Chem 263:14152–14159PubMedGoogle Scholar
  29. 29.
    Baekgaard L, Luoni L, De Michelis MI, Palmgren MG (2006) The plant plasma membrane Ca2+ pump ACA8 contains overlapping as well as physically separated autoinhibitory and calmodulin-binding domains. J Biol Chem 281:1058–1065CrossRefPubMedGoogle Scholar
  30. 30.
    Strehler EE, Strehler-Page M-A, Vogel G, Carafoli E (1989) mRNAs for plasma membrane calcium pumpisoforms differing in their regulatory domain are generated by alternative splicing that involves two internal donor sites in a single exon. Proc Natl Acad Sci USA 86:6908–6912CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Strehler EE, Zacharias DA (2001) Role of alternative splicing in generating isoform diversity among plasma membrane calcium pumps. Physiol Rev 81:21–50CrossRefPubMedGoogle Scholar
  32. 32.
    Krebs J (2015) The plethora of PMCA isoforms: alternative splicing and differential expression. Biochim Biophys Acta 1853:2018–2024CrossRefPubMedGoogle Scholar
  33. 33.
    Tidow H, Hein KL, Baekgaard L, Palmgren MG, Nissen P (2010) Expression, purification, crystallization and preliminary X-ray analysis of calmodulin in complex with the regulatory domain of the plasma membrane Ca2+−ATPase ACA8. Acta Crystallogr Sect F Struct Biol Cryst Commun 66:361–363CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Falchetto R, Vorherr T, Brunner J, Carafoli E (1991) The plasma membrane Ca2+ pump contains a site that interacts with its calmodulin-binding domain. J Biol Chem 266:2930–2936PubMedGoogle Scholar
  35. 35.
    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 1:1613–1621CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Dupont Y (1976) Fluorescence studies of the sarcoplasmic reticulum calcium pump. Biochem Biophys Res Commun 71:544–550CrossRefPubMedGoogle Scholar
  37. 37.
    Krebs J, Vasak M, Scarpa A, Carafoli E (1987) Conformational differences between the E1 and E2 states of the calcium adenosinetriphosphatase of the erythrocyte plasma membrane as revealed by circular dichroism and fluorescence spectroscopy. Biochemistry 26:3921–3926CrossRefPubMedGoogle Scholar
  38. 38.
    Toyoshima C, Nakasako M, Nomura H, Ogawa H (2000) Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 A resolution. Nature 405:647–655CrossRefPubMedGoogle Scholar
  39. 39.
    Toyoshima C (2009) How Ca2+-ATPase pumps ions across the sarcoplasmic reticulum membrane. Biochim Biophys Acta 1793:941–946CrossRefPubMedGoogle Scholar
  40. 40.
    Niggli V, Sigel E, Carafoli E (1982) The purified Ca2+ pump of human erythrocyte membranes catalyzes an electroneutral Ca2+−H+ exchange in reconstituted liposomal systems. J Biol Chem 257:2350–2356PubMedGoogle Scholar
  41. 41.
    Inesi G, Kurzmack M, Coan C, Lewis DE (1980) Cooperative calcium binding and ATPase activation in sarcoplasmic reticulum vesicles. J Biol Chem 255:3025–3031PubMedGoogle Scholar
  42. 42.
    Kosk-Kosicka D, Bzdega T (1988) Activation of the erythrocyte Ca2+-ATPase by either self-association or interaction with calmodulin. J Biol Chem 263:18184–18189PubMedGoogle Scholar
  43. 43.
    Krebs J, Helms V, Griesinger C, Carafoli E (2003) The regulation of the calcium signal by membrane pumps. Helv Chim Acta 86:3875–3888CrossRefGoogle Scholar
  44. 44.
    Schwede T, Kopp J, Guex N, Peitsch MC (2003) SWISS_MODEL: an automated protein homology-modeling server. Nucleic Acids Res 31:3381–3385CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Kataoka M, Head JF, Vorherr T, Krebs J, Carafoli E (1991) Small-angle X-ray scattering study of calmodulin bound to two peptides corresponding to parts of the calmodulin-binding domain of the plasma membrane Ca2+ pump. Biochemistry 30:6247–6251CrossRefPubMedGoogle Scholar
  46. 46.
    Elshorst B et al (1999) NMR solution structure of a complex of calmodulin with a binding peptide of the Ca2+ pump. Biochemistry 38:12320–12332CrossRefPubMedGoogle Scholar
  47. 47.
    Hoeflich KP, Ikura M (2002) Calmodulin in action: diversity in target recognition and activation mechanisms. Cell 108:739–742CrossRefPubMedGoogle Scholar
  48. 48.
    Guerini D, Krebs J, Carafoli E (1984) Stimulation of the purified erythrocyte Ca2+-ATPase by tryptic fragments of calmodulin. J Biol Chem 259:15172–15177PubMedGoogle Scholar
  49. 49.
    Gao ZH, Krebs J, VanBerkum MF, Tang WJ, Maune JF, Means AR, Stull JT, Beckingham K (1993) Activation of four enzymes by two series of calmodulin mutants with point mutations in individual Ca2+ binding sites. J Biol Chem 268:20096–20104PubMedGoogle Scholar
  50. 50.
    Ikura M, Spera S, Barbato G, Kay LE, Krinks M, Bax A (1991) Secundary structure and side-chain1H and 13C resonance assignments of calmodulin in solution by heteronuclear multidimensional NMR spectroscopy. Biochemistry 30:9216–9228CrossRefPubMedGoogle Scholar
  51. 51.
    Ikura M, Barbato G, Klee CB, Bax a (1992) Solution structure of calmodulin and its complex with a myosin light chain kinase fragment. Cell Calcium 13:391–400CrossRefPubMedGoogle Scholar
  52. 52.
    Ikura M, Clore GM, Gronenborn AM, Zhu G, Klee CB, Bax A (1992) Solution structure of a calmodulin-target peptide complex by multidimensional NMR. Science 256:632–638CrossRefPubMedGoogle Scholar
  53. 53.
    Juranic N et al (2010) Calmodulin wraps around its binding domain in the plasma membrane Ca2+ pump anchored by a novel 18-1 motif. J Biol Chem 285:4015–4024CrossRefPubMedGoogle Scholar
  54. 54.
    Carafoli E, Krebs J (2016) Calcium and calmodulin signaling. In: Bradshaw RA, Stahl PD (eds) Encyclopedia of cell biology, vol 3. Elsevier, Waltham, MA, pp 161–169CrossRefGoogle Scholar
  55. 55.
    Enyedi A et al (1994) The Ca2+ affinity of the plasma membrane Ca2+ pump is controlled by alternative splicing. J Biol Chem 269:41–43PubMedGoogle Scholar
  56. 56.
    Silverstein RS, Tempel BL (2006) Atp2b2 encoding plasma membrane Ca2+-ATPase type 2, (PMCA2) exhibits tissue specific first exon usage in hair cells, neurons and mammary glands of mice. Neuroscience 141:245–257CrossRefPubMedGoogle Scholar
  57. 57.
    Brini M, Cali T, Ottolini D, Carafoli E (2013) The plasma membrane calcium pump in health and disease. FEBS J 280:5385–5397CrossRefPubMedGoogle Scholar
  58. 58.
    Prasad V, Okunade GW, Miller ML, Shull GE (2004) Phenotypes of SERCA and PMCA knock out mice. Biochem Biophys Res Commun 322:1192–1203CrossRefPubMedGoogle Scholar
  59. 59.
    Hilfiker H, Guerini D, Carafoli E (1994) Cloning and expression of isoform 2 of the human plasma membrane Ca2+ ATPase. Functional properties of the enzyme and its splicing products. J Biol Chem 269:26178–26183PubMedGoogle Scholar
  60. 60.
    Furuta H, Luo L, Hepler K, Ryan AF (1998) Evidence for differential regulation of calcium by outer versus inner hair cells: plasma membrane Ca-ATPase gene expression. Hear Res 123:10–26CrossRefPubMedGoogle Scholar
  61. 61.
    Dumont RA, Lins U, Filoteo AG, Penniston JT, Kachar B, Gillespie PG (2001) Plasma membrane Ca2+-ATPase isoform 2a is the PMCA of hair bundles. J Neurosci 21:5066–5078PubMedGoogle Scholar
  62. 62.
    Eakin TJ, Antonelli MC, Malchiodi EL, Baskin DG, Stahl WL (1995) Localization of the plasma membrane Ca2+-ATPase isoform PMCA3 in rat cerebellum, choroid plexus and hippocampus. Mol Brain Res 29:71–80CrossRefPubMedGoogle Scholar
  63. 63.
    Stauffer TP, Guerini D, Carafoli E (1995) Tissue distribution of the four gene products of the plasma membrane Ca2+ pump. A study using specific antibodies. J Biol Chem 270:12184–12190CrossRefPubMedGoogle Scholar
  64. 64.
    Greeb J, Shull GE (1989) Molecular cloning of a third isoform of the calmodulin-sensitive plasma membrane Ca2+- transporting ATPase that is expressed predominantly in brain and skeletal muscle. J Biol Chem 264:18569–18576PubMedGoogle Scholar
  65. 65.
    Goellner GM, DeMarco SJ, Strehler EE (2003) Characterization of PISP, a novel single-PDZ protein that binds to all plasma membrane Ca2+-ATPase b-splice variants. Ann NY Acad Sci 986:461–471CrossRefPubMedGoogle Scholar
  66. 66.
    Kim E, DeMarco SJ, Marfatia SM, Chisti AH, Sheng M, Strehler EE (1998) Plasma membrane Ca2+ ATPase isoform 4b binds to membrane-associated guanylate kinase (MAGUK) proteins via their PDZ (PSD95/Dlg/ZO-1) domains. J Biol Chem 273:1591–1595CrossRefPubMedGoogle Scholar
  67. 67.
    Fujimoto T (1993) Calcium pump of the plasma membrane is localized in caveolae. J Cell Biol 120:1147–1157CrossRefPubMedGoogle Scholar
  68. 68.
    Pani B, Singh BB (2009) Lipid rafts/caveolae as microdomains of calcium signaling. Cell Calcium 45:625–633CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Okunade GW et al (2004) Targeted ablation of plasma membrane Ca2+-ATPase (PMCA) 1 and 4 indicates a major housekeeping function for PMCA1 and a critical role in hyperactivated sperm motility and male fertility for PMCA4. J Biol Chem 279:33742–33750CrossRefPubMedGoogle Scholar
  70. 70.
    Brandt P, Neve RL (1992) Expression of plasma membrane calcium-pumping ATPase mRNAs in developing rat brain and adult brain subregions: evidence for stage-specific expression. J Neurochem 59:1566–1569CrossRefPubMedGoogle Scholar
  71. 71.
    Kip SN, Gray NW, Burette A, Canbay A, Weinberg RJ, Strehler EE (2006) Changes in the expression of plasma membrane calcium extrusion systems during the maturation of hippocampal neurons. Hippocampus 16:20–34CrossRefPubMedGoogle Scholar
  72. 72.
    Kenyon KA, Bushong EA, Mauer AS, Strehler EE, Weinberg RJ, Burette AC (2010) Cellular and subcellular localization of the neuron-specific plasma membrane calcium ATPase PMCA1a in the rat brain. J Comp Neurol 518:3169–3183CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Strehler EE, Caride AJ, Filoteo AG, Xiong Y, Penniston JT, Enyedi A (2007) Plasma membrane Ca2+ ATPases as dynamic regulators of cellular calcium handling. Ann NY Acad Sci 1099:226–236CrossRefPubMedGoogle Scholar
  74. 74.
    Krebs J (1998) Calmodulin-dependent protein kinase IV: regulation of function and expression. Biochim Biophys Acta 1448:183–189CrossRefPubMedGoogle Scholar
  75. 75.
    Xie J, Black DL (2001) A CaMKIV responsive RNA element mediates depolarization-induced alternative splicing of ion channels. Nature 410:936–939CrossRefPubMedGoogle Scholar
  76. 76.
    Liu G et al (2012) A conserved serine of heterogeneous nuclear ribonucleoprotein L (hnRNP L) mediates depolarization-regulated alternative splicing of potassium channels. J Biol Chem 287:22709–22716CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Xie J, Calvin J, Stoilov P, Park J, Black DL (2005) A consensus CaMKIV-responsive RNA sequence mediates regulation of alternative exons in neurons. RNA 11:1825–1834CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Krebs J, Means RL, Honegger P (1996) Induction of calmodulin kinase IV by the thyroid hormoneduring the development of rat brain. J Biol Chem 271:11055–11058CrossRefPubMedGoogle Scholar
  79. 79.
    Krebs J (2017) Implications of the thyroid hormone on neuronal development with special emphasis on the calmodulin-kinase IV pathway. Biochim Biophys Acta 1864:877–882CrossRefPubMedGoogle Scholar
  80. 80.
    Street VA, McKee-Johnson JW, Fonseca RC, Tempel BL, Noben-Trauth K (1998) Mutations in a plasma membrane Ca2+-ATPase gene cause deafness in deafwaddler mice. Nat Genet 19:390–394CrossRefPubMedGoogle Scholar
  81. 81.
    Kozel PJ et al (1998) Balance and hearing deficits in mice with a null mutation in the gene encoding plasma membrane Ca2+-ATPase isoform 2. J Biol Chem 273:18693–18696CrossRefPubMedGoogle Scholar
  82. 82.
    Ficarella R et al (2007) A functional study of plasma membrane calcium-pump isoform 2 mutants causing digenic deafness. Proc Natl Acad Sci USA 104:1516–1521CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Reinhardt TA, Horst RL (1999) Ca2+-ATPases and their expression in the mammary gland of pregnant and lactating rats. Am J Phys 276:C796–C802CrossRefGoogle Scholar
  84. 84.
    Jeong J et al (2016) PMCA2 regulates HER2 protein kinase localization and signaling and promotes HER2-mediated breast cancer. Proc Natl Acad Sci USA 113:E282–E290CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Beuschlein F et al (2013) Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension. Nat Genet 45:440–445CrossRefPubMedGoogle Scholar
  86. 86.
    Williams TA et al (2014) Somatic ATP1A1, ATP2B3, and KCNJ5 mutations in aldosterone-producing adenomas. Hypertension 63:188–195CrossRefPubMedGoogle Scholar
  87. 87.
    Zanni G et al (2012) Mutation of plasma membrane Ca2+ ATPase isoform3 in a family with X-linked congenital cerebellar ataxia impairs Ca2+ homeostasis. Proc Natl Acad Sci USA 109:14514–14519CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Wang MG, Yi H, Hilfiker H, Carafoli E, Strehler EE, McBride OW (1994) Localization of two genes encoding plasma membrane Ca2+-ATPases isoforms 2 (ATP2B2) and 3 (ATP2B3) to human chromosomes 3p26-25 and Xq28, respectively. Cytogenet Cell Genet 67:41–45CrossRefPubMedGoogle Scholar
  89. 89.
    Feyma T et al (2016) Dystonia in ATP2B3-associated X-linked spinocerebellar ataxia. Mov Disord 31:1752–1753CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Tatsuki F et al (2016) Involvement of Ca(2+)-dependent hyperpolarization in sleep duration in mammals. Neuron 90:70–85CrossRefPubMedGoogle Scholar
  91. 91.
    Wennemuth G, Babcock DF, Hille B (2003) Calcium clearance mechanisms of mouse sperm. J Cell Biol 122:115–128Google Scholar
  92. 92.
    Schuh K et al (2004) Plasma membrane Ca2+ ATPase 4 is required for sperm motility and male fertility. J Biol Chem 279:28220–28226CrossRefPubMedGoogle Scholar
  93. 93.
    Brandenburger T et al (2011) Switch of PMCA4 splice variants in bovine epididymis results in altered isoform expression during functional sperm maturation. J Biol Chem 286:7938–7946CrossRefPubMedGoogle Scholar
  94. 94.
    Prasad V et al (2014) Ablation of plasma membrane Ca2+-ATPase isoform 4 prevents development of hypertrophy in a model of hypertrophyc cardiomyopathy. J Mol Cell Cardiol 77:53–63CrossRefPubMedGoogle Scholar
  95. 95.
    Wu X et al (2009) Plasma membrane Ca2+-ATPase isoform 4 antagonizes cardiac hypertrophy in association with calcineurin inhibition in rodents. J Clin Invest 119:976–985PubMedPubMedCentralGoogle Scholar
  96. 96.
    Ho PW, Pang SY, Li M, Tse ZH, Kung MH, Sham PC, Ho SL (2015) PMCA4 (ATP2B4) mutation in familial spastic paraplegia causes delay in intracellular calcium extrusion. Brain Behav 5:e00321CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Li M, Ho PW, Pang SY, Tse ZH, Kung MH, Sham PC, Ho SL (2014) PMCA4 (ATP2B4) mutation in familial spastic paraplegia. PLoS One 9:e104790CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Marques-da-Silva D, Gutierrez-Merino C (2014) Caveolin-rich lipid rafts of the plasma membrane of mature cerebellar granule neurons are microcompartments for calcium/reactive oxygen and nitrogen species cross-talk signaling. Cell Calcium 56:108–123CrossRefPubMedGoogle Scholar
  99. 99.
    Schuh K, Uldrijan S, Telkamp M, Röthlein N, Neyses L (2001) The plasma membrane calmodulin-dependent calcium pump: a major regulator of nitric oxide synthase I. J Cell Biol 155:201–205CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Oceandy D et al (2007) Neuronal nitric oxide synthase signaling in the heart is regulated by the sarcolemmal calcium pump 4b. Circulation 115:483–492CrossRefPubMedGoogle Scholar
  101. 101.
    Mohamed TM et al (2011) Plasma membrane calcium pump (PMCA4)-neuronal nitric-oxide synthase complex regulates cardiac contractility through modulation of a compartmentalized cyclic nucleotide microdomain. J Biol Chem 286:41520–41529CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Bozulik LD, Malik MT, Powell DW, Nanez A, Link AJ, Ramos KS, Dean WL (2007) Plasma membrane Ca(2+)-ATPase associates with CLP36, alpha-actinin, and actin in human platelets. Thromb Haemost 97:587–597CrossRefGoogle Scholar
  103. 103.
    Kruger WA, Yun CC, Monteith GR, Poronnik P (2009) Muscarinic-induced recruitment of plasma membrane Ca2+-ATPase involves PSD-95/Dlg/Zo-1-mediated interactions. J Biol Chem 284:1820–1830CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Gomez-Varela D, Schmidt M, Schoellermann J, Peters EC, Berg DK (2012) PMCA2 via PSD-95 controls calcium signaling by α7-containing nicotinic acetylcholine receptors on aspiny interneurons. J Neurosci 32:6894–6905CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Carafoli E, Zurini M (1982) The Ca2+-pumping ATPase of plasma membranes: purification, reconstitution and properties. Biochim Biophys Acta 683:279–301CrossRefPubMedGoogle Scholar
  106. 106.
    Choquette D, Hakim G, Filoteo AG, Plishker GA, Bostwick JR, Penniston JT (1984) Regulation of plasma membrane Ca2+ ATPases by lipids of the phosphatidylinositol cycle. Biochem Biophys Res Commun 125:908–915CrossRefPubMedGoogle Scholar
  107. 107.
    Ambudkar IS, de Souza LB, Ong HL (2017) TRPC1, Orai 1, and STIM1 in SOCE: friends in tight spaces. Cell Calcium 63:33–39CrossRefPubMedGoogle Scholar
  108. 108.
    Hogan PG, Rao A (2015) Store-operated calcium entry: mechanisms and modulation. Biochem Biophys Res Commun 460:40–49CrossRefPubMedPubMedCentralGoogle Scholar
  109. 109.
    Maleth J, Choi S, Muallem S, Ahuja M (2015) Translocation of PI(4,5) P2-poor and PI(4,5)P2-rich microdomains during store depletion determines STIM1 conformation and Orai1 gating. Nat Commun 5:5843CrossRefGoogle Scholar
  110. 110.
    Liou J, Fivaz M, Inoue T, Meyer T (2007) Live-cell imaging reveals sequential oligomerization and local plasma membrane targeting of stromal interaction molecule 1 after Ca2+ store depletion. Proc Natl Acad Sci USA 104:9301–9306CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    Ong HL, Ambudkar IS (2011) The dynamic complexity of the TRPC1 channelosome. Channels 5:424–431CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Max Planck Institute for Biophysical ChemistryGöttingenGermany

Personalised recommendations