Pflügers Archiv - European Journal of Physiology

, Volume 457, Issue 3, pp 687–700

The role of SERCA2a/PLN complex, Ca2+ homeostasis, and anti-apoptotic proteins in determining cell fate

  • Elizabeth Vafiadaki
  • Vasiliki Papalouka
  • Demetrios A. Arvanitis
  • Evangelia G. Kranias
  • Despina Sanoudou
Cardiovascular Physiology

Abstract

Intracellular calcium is a major coordinator of numerous aspects of cellular physiology, including muscle contractility and cell survival. In cardiac muscle, aberrant Ca2+ cycling has been implicated in a range of pathological conditions including cardiomyopathies and heart failure. The sarco(endo)plasmic reticulum Ca2+ transport adenosine triphosphatase (SERCA2a) and its regulator phospholamban (PLN) have a central role in modulating Ca2+ homeostasis and, therefore, cardiac function. Herein, we discuss the mechanisms through which SERCA2a and PLN control cardiomyocyte function in health and disease. Emphasis is placed on our newly identified PLN-binding partner HS-1-associated protein X-1 (HAX-1), which has an anti-apoptotic function and presents with numerous similarities to Bcl-2. Recent evidence indicates that proteins of the Bcl-2 family can influence ER Ca2+ content, a critical determinant of cellular sensitivity to apoptosis. The discovery of the PLN/HAX-1 interaction therefore unveils an important new link between Ca2+ homeostasis and cell survival, with significant therapeutic potential.

Keywords

Ca2+ regulation Sarcoplasmic reticulum Mitochondria Cardiac function Calcium ATPase Apoptosis 

References

  1. 1.
    Fabiato A, Fabiato F (1979) Calcium and cardiac excitation–contraction coupling. Annu Rev Physiol 41:473–84PubMedCrossRefGoogle Scholar
  2. 2.
    Lederer WJ, Berlin JR, Cohen NM, Hadley RW, Bers DM, Cannell MB (1990) Excitation–contraction coupling in heart cells. Roles of the sodium–calcium exchange, the calcium current, and the sarcoplasmic reticulum. Ann NY Acad Sci 588:190–206PubMedCrossRefGoogle Scholar
  3. 3.
    Bers DM (2002) Cardiac excitation–contraction coupling. Nature 415:198–205PubMedCrossRefGoogle Scholar
  4. 4.
    Bers DM (2002) Calcium and cardiac rhythms: physiological and pathophysiological. Circ Res 90:14–17PubMedGoogle Scholar
  5. 5.
    Houser SR, Piacentino V III, Weisser J (2000) Abnormalities of calcium cycling in the hypertrophied and failing heart. J Mol Cell Cardiol 32:1595–1607PubMedCrossRefGoogle Scholar
  6. 6.
    Dash R, Frank KF, Carr AN, Moravec CS, Kranias EG (2001) Gender influences on sarcoplasmic reticulum Ca2+-handling in failing human myocardium. J Mol Cell Cardiol 33:1345–1353PubMedCrossRefGoogle Scholar
  7. 7.
    Hasenfuss G, Pieske B (2002) Calcium cycling in congestive heart failure. J Mol Cell Cardiol 34:951–969PubMedCrossRefGoogle Scholar
  8. 8.
    Gustafsson AB, Gottlieb RA (2007) Bcl-2 family members and apoptosis, taken to heart. Am J Physiol Cell Physiol 292:C45–C51PubMedCrossRefGoogle Scholar
  9. 9.
    Kang PM, Izumo S (2000) Apoptosis and heart failure: a critical review of the literature. Circ Res 86:1107–1113PubMedGoogle Scholar
  10. 10.
    Narula J, Kolodgie FD, Virmani R (2000) Apoptosis and cardiomyopathy. Curr Opin Cardiol 15:183–188PubMedCrossRefGoogle Scholar
  11. 11.
    Gill C, Mestril R, Samali A (2002) Losing heart: the role of apoptosis in heart disease—a novel therapeutic target? FASEB J 16:135–146PubMedCrossRefGoogle Scholar
  12. 12.
    Narula J, Haider N, Arbustini E, Chandrashekhar Y (2006) Mechanisms of disease: apoptosis in heart failure—seeing hope in death. Nat Clin Pract Cardiovasc Med 3:681–688PubMedCrossRefGoogle Scholar
  13. 13.
    Khoynezhad A, Jalali Z, Tortolani AJ (2007) A synopsis of research in cardiac apoptosis and its application to congestive heart failure. Tex Heart Inst J 34:352–359PubMedGoogle Scholar
  14. 14.
    Lytton J, Zarain-Herzberg A, Periasamy M, MacLennan DH (1989) Molecular cloning of the mammalian smooth muscle sarco(endo)plasmic reticulum Ca2+-ATPase. J Biol Chem 264:7059–7065PubMedGoogle Scholar
  15. 15.
    Zarain-Herzberg A, MacLennan DH, Periasamy M (1990) Characterization of rabbit cardiac sarco(endo)plasmic reticulum Ca2(+)-ATPase gene. J Biol Chem 265:4670–4677PubMedGoogle Scholar
  16. 16.
    MacLennan DH, Rice WJ, Green NM (1997) The mechanism of Ca2+ transport by sarco(endo)plasmic reticulum Ca2+-ATPases. J Biol Chem 272:28815–28818PubMedCrossRefGoogle Scholar
  17. 17.
    Campbell AM, Kessler PD, Sagara Y, Inesi G, Fambrough DM (1991) Nucleotide sequences of avian cardiac and brain SR/ER Ca(2+)-ATPases and functional comparisons with fast twitch Ca(2+)-ATPase. Calcium affinities and inhibitor effects. J Biol Chem 266:16050–16055PubMedGoogle Scholar
  18. 18.
    Asahi M, Nakayama H, Tada M, Otsu K (2003) Regulation of sarco(endo)plasmic reticulum Ca2+ adenosine triphosphatase by phospholamban and sarcolipin: implication for cardiac hypertrophy and failure. Trends Cardiovasc Med 13:152–157PubMedCrossRefGoogle Scholar
  19. 19.
    He H, Giordano FJ, Hilal-Dandan R, Choi DJ, Rockman HA, McDonough PM, Bluhm WF, Meyer M, Sayen MR, Swanson E, Dillmann WH (1997) Overexpression of the rat sarcoplasmic reticulum Ca2+ ATPase gene in the heart of transgenic mice accelerates calcium transients and cardiac relaxation. J Clin Invest 100:380–389PubMedCrossRefGoogle Scholar
  20. 20.
    Baker DL, Hashimoto K, Grupp IL, Ji Y, Reed T, Loukianov E, Grupp G, Bhagwhat A, Hoit B, Walsh R, Marban E, Periasamy M (1998) Targeted overexpression of the sarcoplasmic reticulum Ca2+-ATPase increases cardiac contractility in transgenic mouse hearts. Circ Res 83:1205–1214PubMedGoogle Scholar
  21. 21.
    Vetter R, Rehfeld U, Reissfelder C, Weiss W, Wagner KD, Gunther J, Hammes A, Tschope C, Dillmann W, Paul M (2002) Transgenic overexpression of the sarcoplasmic reticulum Ca2+ ATPase improves reticular Ca2+ handling in normal and diabetic rat hearts. FASEB J 16:1657–1659PubMedGoogle Scholar
  22. 22.
    Periasamy M, Reed TD, Liu LH, Ji Y, Loukianov E, Paul RJ, Nieman ML, Riddle T, Duffy JJ, Doetschman T, Lorenz JN, Shull GE (1999) Impaired cardiac performance in heterozygous mice with a null mutation in the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 (SERCA2) gene. J Biol Chem 274:2556–2562PubMedCrossRefGoogle Scholar
  23. 23.
    Schultz Jel J, Glascock BJ, Witt SA, Nieman ML, Nattamai KJ, Liu LH, Lorenz JN, Shull GE, Kimball TR, Periasamy M (2004) Accelerated onset of heart failure in mice during pressure overload with chronically decreased SERCA2 calcium pump activity. Am J Physiol Heart Circ Physiol 286:H1146–H1153PubMedCrossRefGoogle Scholar
  24. 24.
    Ji Y, Lalli MJ, Babu GJ, Xu Y, Kirkpatrick DL, Liu LH, Chiamvimonvat N, Walsh RA, Shull GE, Periasamy M (2000) Disruption of a single copy of the SERCA2 gene results in altered Ca2+ homeostasis and cardiomyocyte function. J Biol Chem 275:38073–38080PubMedCrossRefGoogle Scholar
  25. 25.
    Schmidt AG, Haghighi K, Frank B, Pater L, Dorn GW, Walsh RA, Kranias EG (2003) Polymorphic SERCA2a variants do not account for inter-individual differences in phospholamban–SERCA2a interactions in human heart failure. J Mol Cell Cardiol 35:867–870PubMedCrossRefGoogle Scholar
  26. 26.
    Miyauchi Y, Daiho T, Yamasaki K, Takahashi H, Ishida-Yamamoto A, Danko S, Suzuki H, Iizuka H (2006) Comprehensive analysis of expression and function of 51 sarco(endo)plasmic reticulum Ca2+-ATPase mutants associated with Darier disease. J Biol Chem 281:22882–22895PubMedCrossRefGoogle Scholar
  27. 27.
    Sakuntabhai A, Ruiz-Perez V, Carter S, Jacobsen N, Burge S, Monk S, Smith M, Munro CS, O'Donovan M, Craddock N, Kucherlapati R, Rees JL, Owen M, Lathrop GM, Monaco AP, Strachan T, Hovnanian A (1999) Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease. Nat Genet 21:271–277PubMedCrossRefGoogle Scholar
  28. 28.
    Ruiz-Perez VL, Carter SA, Healy E, Todd C, Rees JL, Steijlen PM, Carmichael AJ, Lewis HM, Hohl D, Itin P, Vahlquist A, Gobello T, Mazzanti C, Reggazini R, Nagy G, Munro CS, Strachan T (1999) ATP2A2 mutations in Darier’s disease: variant cutaneous phenotypes are associated with missense mutations, but neuropsychiatric features are independent of mutation class. Hum Mol Genet 8:1621–1630PubMedCrossRefGoogle Scholar
  29. 29.
    Nagai R, Zarain-Herzberg A, Brandl CJ, Fujii J, Tada M, MacLennan DH, Alpert NR, Periasamy M (1989) Regulation of myocardial Ca2+-ATPase and phospholamban mRNA expression in response to pressure overload and thyroid hormone. Proc Natl Acad Sci USA 86:2966–2970PubMedCrossRefGoogle Scholar
  30. 30.
    Zarain-Herzberg A, Afzal N, Elimban V, Dhalla NS (1996) Decreased expression of cardiac sarcoplasmic reticulum Ca(2+)-pump ATPase in congestive heart failure due to myocardial infarction. Mol Cell Biochem 163–164:285–290PubMedCrossRefGoogle Scholar
  31. 31.
    O'Rourke B, Kass DA, Tomaselli GF, Kaab S, Tunin R, Marban E (1999) Mechanisms of altered excitation-contraction coupling in canine tachycardia-induced heart failure, I: experimental studies. Circ Res 84:562–570PubMedGoogle Scholar
  32. 32.
    Arai M, Alpert NR, MacLennan DH, Barton P, Periasamy M (1993) Alterations in sarcoplasmic reticulum gene expression in human heart failure. A possible mechanism for alterations in systolic and diastolic properties of the failing myocardium. Circ Res 72:463–469PubMedGoogle Scholar
  33. 33.
    Arai M, Matsui H, Periasamy M (1994) Sarcoplasmic reticulum gene expression in cardiac hypertrophy and heart failure. Circ Res 74:555–564PubMedGoogle Scholar
  34. 34.
    Hasenfuss G, Reinecke H, Studer R, Meyer M, Pieske B, Holtz J, Holubarsch C, Posival H, Just H, Drexler H (1994) Relation between myocardial function and expression of sarcoplasmic reticulum Ca(2+)-ATPase in failing and nonfailing human myocardium. Circ Res 75:434–442PubMedGoogle Scholar
  35. 35.
    Hasenfuss G (1998) Alterations of calcium-regulatory proteins in heart failure. Cardiovasc Res 37:279–289PubMedCrossRefGoogle Scholar
  36. 36.
    Pieske B, Maier LS, Bers DM, Hasenfuss G (1999) Ca2+ handling and sarcoplasmic reticulum Ca2+ content in isolated failing and nonfailing human myocardium. Circ Res 85:38–46PubMedGoogle Scholar
  37. 37.
    Meyer M, Schillinger W, Pieske B, Holubarsch C, Heilmann C, Posival H, Kuwajima G, Mikoshiba K, Just H, Hasenfuss G et al (1995) Alterations of sarcoplasmic reticulum proteins in failing human dilated cardiomyopathy. Circulation 92:778–784PubMedGoogle Scholar
  38. 38.
    Arvanitis DA, Vafiadaki E, Fan GC, Mitton BA, Gregory KN, Del Monte F, Kontrogianni-Konstantopoulos A, Sanoudou D, Kranias EG (2007) Histidine-rich Ca-binding protein interacts with sarcoplasmic reticulum Ca-ATPase. Am J Physiol Heart Circ Physiol 293:H1581–H1589PubMedCrossRefGoogle Scholar
  39. 39.
    Ihara Y, Kageyama K, Kondo T (2005) Overexpression of calreticulin sensitizes SERCA2a to oxidative stress. Biochem Biophys Res Commun 329:1343–1349PubMedCrossRefGoogle Scholar
  40. 40.
    Kiewitz R, Acklin C, Schafer BW, Maco B, Uhrik B, Wuytack F, Erne P, Heizmann CW (2003) Ca2+-dependent interaction of S100A1 with the sarcoplasmic reticulum Ca2+-ATPase2a and phospholamban in the human heart. Biochem Biophys Res Commun 306:550–557PubMedCrossRefGoogle Scholar
  41. 41.
    Nediani C, Celli A, Fiorillo C, Ponziani V, Giannini L, Nassi P (2003) Acylphosphatase interferes with SERCA2a-PLN association. Biochem Biophys Res Commun 301:948–951PubMedCrossRefGoogle Scholar
  42. 42.
    Dremina ES, Sharov VS, Kumar K, Zaidi A, Michaelis EK, Schoneich C (2004) Anti-apoptotic protein Bcl-2 interacts with and destabilizes the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA). Biochem J 383:361–370PubMedCrossRefGoogle Scholar
  43. 43.
    Kuo TH, Kim HR, Zhu L, Yu Y, Lin HM, Tsang W (1998) Modulation of endoplasmic reticulum calcium pump by Bcl-2. Oncogene 17:1903–1910PubMedCrossRefGoogle Scholar
  44. 44.
    Bhupathy P, Babu GJ, Periasamy M (2007) Sarcolipin and phospholamban as regulators of cardiac sarcoplasmic reticulum Ca2+ ATPase. J Mol Cell Cardiol 42:903–911PubMedCrossRefGoogle Scholar
  45. 45.
    Simmerman HK, Jones LR (1998) Phospholamban: protein structure, mechanism of action, and role in cardiac function. Physiol Rev 78:921–947PubMedGoogle Scholar
  46. 46.
    Kadambi VJ, Kranias EG (1997) Phospholamban: a protein coming of age. Biochem Biophys Res Commun 239:1–5PubMedCrossRefGoogle Scholar
  47. 47.
    MacLennan DH, Kranias EG (2003) Phospholamban: a crucial regulator of cardiac contractility. Nat Rev Mol Cell Biol 4:566–577PubMedCrossRefGoogle Scholar
  48. 48.
    Fujii J, Ueno A, Kitano K, Tanaka S, Kadoma M, Tada M (1987) Complete complementary DNA-derived amino acid sequence of canine cardiac phospholamban. J Clin Invest 79:301–304PubMedCrossRefGoogle Scholar
  49. 49.
    James P, Inui M, Tada M, Chiesi M, Carafoli E (1989) Nature and site of phospholamban regulation of the Ca2+ pump of sarcoplasmic reticulum. Nature 342:90–92PubMedCrossRefGoogle Scholar
  50. 50.
    Toyofuku T, Kurzydlowski K, Tada M, MacLennan DH (1994) Amino acids Lys–Asp–Asp–Lys–Pro–Val402 in the Ca(2+)-ATPase of cardiac sarcoplasmic reticulum are critical for functional association with phospholamban. J Biol Chem 269:22929–22932PubMedGoogle Scholar
  51. 51.
    Toyofuku T, Kurzydlowski K, Tada M, MacLennan DH (1994) Amino acids Glu2 to Ile18 in the cytoplasmic domain of phospholamban are essential for functional association with the Ca(2+)-ATPase of sarcoplasmic reticulum. J Biol Chem 269:3088–3094PubMedGoogle Scholar
  52. 52.
    Sharma P, Patchell VB, Gao Y, Evans JS, Levine BA (2001) Cytoplasmic interactions between phospholamban residues 1–20 and the calcium-activated ATPase of the sarcoplasmic reticulum. Biochem J 335:699–706Google Scholar
  53. 53.
    Kimura Y, Asahi M, Kurzydlowski K, Tada M, MacLennan DH (1998) Phospholamban domain Ib mutations influence functional interactions with the Ca2+-ATPase isoform of cardiac sarcoplasmic reticulum. J Biol Chem 273:14238–14241PubMedCrossRefGoogle Scholar
  54. 54.
    Chen Z, Stokes DL, Jones LR (2005) Role of leucine 31 of phospholamban in structural and functional interactions with the Ca2+ pump of cardiac sarcoplasmic reticulum. J Biol Chem 280:10530–10539PubMedCrossRefGoogle Scholar
  55. 55.
    Morris GL, Cheng HC, Colyer J, Wang JH (1991) Phospholamban regulation of cardiac sarcoplasmic reticulum (Ca(2+)-Mg2+)-ATPase. Mechanism of regulation and site of monoclonal antibody interaction. J Biol Chem 266:11270–11275PubMedGoogle Scholar
  56. 56.
    Wegener AD, Simmerman HK, Lindemann JP, Jones LR (1989) Phospholamban phosphorylation in intact ventricles. Phosphorylation of serine 16 and threonine 17 in response to beta-adrenergic stimulation. J Biol Chem 264:11468–11474PubMedGoogle Scholar
  57. 57.
    Kimura Y, Kurzydlowski K, Tada M, MacLennan DH (1997) Phospholamban inhibitory function is activated by depolymerization. J Biol Chem 272:15061–15064PubMedCrossRefGoogle Scholar
  58. 58.
    Zvaritch E, Backx PH, Jirik F, Kimura Y, de Leon S, Schmidt AG, Hoit BD, Lester JW, Kranias EG, MacLennan DH (2000) The transgenic expression of highly inhibitory monomeric forms of phospholamban in mouse heart impairs cardiac contractility. J Biol Chem 275:14985–14991PubMedCrossRefGoogle Scholar
  59. 59.
    Cantilina T, Sagara Y, Inesi G, Jones LR (1993) Comparative studies of cardiac and skeletal sarcoplasmic reticulum ATPases. Effect of a phospholamban antibody on enzyme activation by Ca2+. J Biol Chem 268:17018–17025PubMedGoogle Scholar
  60. 60.
    Inui M, Chamberlain BK, Saito A, Fleischer S (1986) The nature of the modulation of Ca2+ transport as studied by reconstitution of cardiac sarcoplasmic reticulum. J Biol Chem 261:1794–1800PubMedGoogle Scholar
  61. 61.
    Tada M, Katz AM (1982) Phosphorylation of the sarcoplasmic reticulum and sarcolemma. Annu Rev Physiol 44:401–423PubMedCrossRefGoogle Scholar
  62. 62.
    Slack JP, Grupp IL, Dash R, Holder D, Schmidt A, Gerst MJ, Tamura T, Tilgmann C, James PF, Johnson R, Gerdes AM, Kranias EG (2001) The enhanced contractility of the phospholamban-deficient mouse heart persists with aging. J Mol Cell Cardiol 33:1031–1040PubMedCrossRefGoogle Scholar
  63. 63.
    Luo W, Grupp IL, Harrer J, Ponniah S, Grupp G, Duffy JJ, Doetschman T, Kranias EG (1994) Targeted ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of beta-agonist stimulation. Circ Res 75:401–409PubMedGoogle Scholar
  64. 64.
    Kiss E, Edes I, Sato Y, Luo W, Liggett SB, Kranias EG (1997) Beta-adrenergic regulation of cAMP and protein phosphorylation in phospholamban-knockout mouse hearts. Am J Physiol 272:H785–H790PubMedGoogle Scholar
  65. 65.
    Lorenz JN, Kranias EG (1997) Regulatory effects of phospholamban on cardiac function in intact mice. Am J Physiol 273:H2826–H2831PubMedGoogle Scholar
  66. 66.
    Luo W, Wolska BM, Grupp IL, Harrer JM, Haghighi K, Ferguson DG, Slack JP, Grupp G, Doetschman T, Solaro RJ, Kranias EG (1996) Phospholamban gene dosage effects in the mammalian heart. Circ Res 78:839–847PubMedGoogle Scholar
  67. 67.
    Zhai J, Schmidt AG, Hoit BD, Kimura Y, MacLennan DH, Kranias EG (2000) Cardiac-specific overexpression of a superinhibitory pentameric phospholamban mutant enhances inhibition of cardiac function in vivo. J Biol Chem 275:10538–10544PubMedCrossRefGoogle Scholar
  68. 68.
    Haghighi K, Schmidt AG, Hoit BD, Brittsan AG, Yatani A, Lester JW, Zhai J, Kimura Y, Dorn GW II, MacLennan DH, Kranias EG (2001) Superinhibition of sarcoplasmic reticulum function by phospholamban induces cardiac contractile failure. J Biol Chem 276:24145–24152PubMedCrossRefGoogle Scholar
  69. 69.
    Schmidt AG, Zhai J, Carr AN, Gerst MJ, Lorenz JN, Pollesello P, Annila A, Hoit BD, Kranias EG (2002) Structural and functional implications of the phospholamban hinge domain: impaired SR Ca2+ uptake as a primary cause of heart failure. Cardiovasc Res 56:248–259PubMedCrossRefGoogle Scholar
  70. 70.
    Luo W, Chu G, Sato Y, Zhou Z, Kadambi VJ, Kranias EG (1998) Transgenic approaches to define the functional role of dual site phospholamban phosphorylation. J Biol Chem 273:4734–4739PubMedCrossRefGoogle Scholar
  71. 71.
    Kuschel M, Karczewski P, Hempel P, Schlegel WP, Krause EG, Bartel S (1999) Ser16 prevails over Thr17 phospholamban phosphorylation in the beta-adrenergic regulation of cardiac relaxation. Am J Physiol 276:H1625–H1633PubMedGoogle Scholar
  72. 72.
    Chu G, Lester JW, Young KB, Luo W, Zhai J, Kranias EG (2000) A single site (Ser16) phosphorylation in phospholamban is sufficient in mediating its maximal cardiac responses to beta -agonists. J Biol Chem 275:38938–38943PubMedCrossRefGoogle Scholar
  73. 73.
    Zhao W, Uehara Y, Chu G, Song Q, Qian J, Young K, Kranias EG (2004) Threonine-17 phosphorylation of phospholamban: a key determinant of frequency-dependent increase of cardiac contractility. J Mol Cell Cardiol 37:607–612PubMedCrossRefGoogle Scholar
  74. 74.
    Schmitt JP, Kamisago M, Asahi M, Li GH, Ahmad F, Mende U, Kranias EG, MacLennan DH, Seidman JG, Seidman CE (2003) Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban. Science 299:1410–1413PubMedCrossRefGoogle Scholar
  75. 75.
    Haghighi K, Kolokathis F, Gramolini AO, Waggoner JR, Pater L, Lynch RA, Fan GC, Tsiapras D, Parekh RR, Dorn GWn, Maclennan DH, Kremastinos DT, Kranias EG (2006) A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy. Proc Natl Acad Sci USA 103:1388–1393PubMedCrossRefGoogle Scholar
  76. 76.
    Haghighi K, Kolokathis F, Pater L, Lynch RA, Asahi M, Gramolini AO, Fan GC, Tsiapras D, Hahn HS, Adamopoulos S, Liggett SB, Dorn GWn, MacLennan DH, Kremastinos DT, Kranias EG (2003) Human phospholamban null results in lethal dilated cardiomyopathy revealing a critical difference between mouse and human. J Clin Invest 111:869–876PubMedGoogle Scholar
  77. 77.
    Haghighi K, Chen G, Sato Y, Fan GC, He S, Kolokathis F, Pater L, Paraskevaidis I, Jones WK, Dorn Ii GW, Th Kremastinos D, Kranias EG (2008) A human phospholamban promoter polymorphism in dilated cardiomyopathy alters transcriptional regulation by glucocorticoids. Hum Mutat (in press)Google Scholar
  78. 78.
    Minamisawa S, Sato Y, Tatsuguchi Y, Fujino T, Imamura S, Uetsuka Y, Nakazawa M, Matsuoka R (2003) Mutation of the phospholamban promoter associated with hypertrophic cardiomyopathy. Biochem Biophys Res Commun 304:1–4PubMedCrossRefGoogle Scholar
  79. 79.
    Medin M, Hermida-Prieto M, Monserrat L, Laredo R, Rodriguez-Rey JC, Fernandez X, Castro-Beiras A (2007) Mutational screening of phospholamban gene in hypertrophic and idiopathic dilated cardiomyopathy and functional study of the PLN −42 C>G mutation. Eur J Heart Fail 9:37–43PubMedCrossRefGoogle Scholar
  80. 80.
    Zhao W, Yuan Q, Qian J, Waggoner JR, Pathak A, Chu G, Mitton B, Sun X, Jin J, Braz JC, Hahn HS, Marreez Y, Syed F, Pollesello P, Annila A, Wang HS, Schultz Jel J, Molkentin JD, Liggett SB, Dorn GW II, Kranias EG (2006) The presence of Lys27 instead of Asn27 in human phospholamban promotes sarcoplasmic reticulum Ca2+-ATPase superinhibition and cardiac remodeling. Circulation 113:995–1004PubMedCrossRefGoogle Scholar
  81. 81.
    Vafiadaki E, Sanoudou D, Arvanitis DA, Catino DH, Kranias EG, Kontrogianni-Konstantopoulos A (2007) Phospholamban interacts with HAX-1, a mitochondrial protein with anti-apoptotic function. J Mol Biol 367:65–79PubMedCrossRefGoogle Scholar
  82. 82.
    Suzuki Y, Demoliere C, Kitamura D, Takeshita H, Deuschle U, Watanabe T (1997) HAX-1, a novel intracellular protein, localized on mitochondria, directly associates with HS1, a substrate of Src family of tyrosine kinases. J Immunol 158:2736–2744PubMedGoogle Scholar
  83. 83.
    Kawaguchi Y, Nakajima K, Igarashi M, Morita T, Tanaka M, Suzuki M, Yokoyama A, Matsuda G, Kato K, Kanamori M, Hirai K (2000) Interaction of Epstein–Barr virus nuclear antigen leader protein (EBNA-LP) with HS1-associated protein X-1: implication of cytoplasmic function of EBNA-LP. J Virol 74:10104–10111PubMedCrossRefGoogle Scholar
  84. 84.
    Matsuda G, Nakajima K, Kawaguchi Y, Yamanashi Y, Hirai K (2003) Epstein–Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) forms complexes with a cellular anti-apoptosis protein Bcl-2 or its EBV counterpart BHRF1 through HS1-associated protein X-1. Microbiol Immunol 47:91–99PubMedGoogle Scholar
  85. 85.
    Sharp TV, Wang HW, Koumi A, Hollyman D, Endo Y, Ye H, Du MQ, Boshoff C (2002) K15 protein of Kaposi’s sarcoma-associated herpesvirus is latently expressed and binds to HAX-1, a protein with antiapoptotic function. J Virol 76:802–816PubMedCrossRefGoogle Scholar
  86. 86.
    Yedavalli VS, Shih HM, Chiang YP, Lu CY, Chang LY, Chen MY, Chuang CY, Dayton AI, Jeang KT, Huang LM (2005) Human immunodeficiency virus type 1 Vpr interacts with antiapoptotic mitochondrial protein HAX-1. J Virol 79:13735–13746PubMedCrossRefGoogle Scholar
  87. 87.
    Modem S, Reddy TR (2008) An anti-apoptotic protein, Hax-1, inhibits the HIV-1 rev function by altering its sub-cellular localization. J Cell Physiol 214:14–19PubMedCrossRefGoogle Scholar
  88. 88.
    Dufva M, Olsson M, Rymo L (2001) Epstein–Barr virus nuclear antigen 5 interacts with HAX-1, a possible component of the B-cell receptor signalling pathway. J Gen Virol 82:1581–1587PubMedGoogle Scholar
  89. 89.
    Gallagher AR, Cedzich A, Gretz N, Somlo S, Witzgall R (2000) The polycystic kidney disease protein PKD2 interacts with Hax-1, a protein associated with the actin cytoskeleton. Proc Natl Acad Sci USA 97:4017–4022PubMedCrossRefGoogle Scholar
  90. 90.
    Radhika V, Onesime D, Ha JH, Dhanasekaran N (2004) Galpha13 stimulates cell migration through cortactin-interacting protein Hax-1. J Biol Chem 279:49406–49413PubMedCrossRefGoogle Scholar
  91. 91.
    Ramsay AG, Keppler MD, Jazayeri M, Thomas GJ, Parsons M, Violette S, Weinreb P, Hart IR, Marshall JF (2007) HS1-associated protein X-1 regulates carcinoma cell migration and invasion via clathrin-mediated endocytosis of integrin alphavbeta6. Cancer Res 67:5275–5284PubMedCrossRefGoogle Scholar
  92. 92.
    Yin H, Morioka H, Towle CA, Vidal M, Watanabe T, Weissbach L (2001) Evidence that HAX-1 is an interleukin-1 alpha N-terminal binding protein. Cytokine 15:122–137PubMedCrossRefGoogle Scholar
  93. 93.
    Kawaguchi Y, Nishimagi E, Tochimoto A, Kawamoto M, Katsumata Y, Soejima M, Kanno T, Kamatani N, Hara M (2006) Intracellular IL-1{alpha}-binding proteins contribute to biological functions of endogenous IL-1{alpha} in systemic sclerosis fibroblasts. Proc Natl Acad Sci USA 103:14501–14506PubMedCrossRefGoogle Scholar
  94. 94.
    Ortiz DF, Moseley J, Calderon G, Swift AL, Li S, Arias IM (2004) Identification of HAX-1 as a protein that binds bile salt export protein and regulates its abundance in the apical membrane of Madin–Darby canine kidney cells. J Biol Chem 279:32761–32770PubMedCrossRefGoogle Scholar
  95. 95.
    Kasashima K, Ohta E, Kagawa Y, Endo H (2006) The pleiotropic human prohibitin 2: mitochondrial functions and estrogen receptor-dependent nuclear translocation. J Biol Chem 281:36401–36410PubMedCrossRefGoogle Scholar
  96. 96.
    Han Y, Chen Y-S, Liu Z, Bodyak N, Rigor D, Bisping E, Pu WT, Kang PM (2006) Overexpression of HAX-1 protects cardiac myocytes from apoptosis through caspase-9 inhibition. Circ Res 99:415–423PubMedCrossRefGoogle Scholar
  97. 97.
    Cilenti L, Soundarapandian MM, Kyriazis GA, Stratico V, Singh S, Gupta S, Bonventre JV, Alnemri ES, Zervos AS (2004) Regulation of HAX-1 anti-apoptotic protein by Omi/HtrA2 protease during cell death. J Biol Chem 279:50295–50301PubMedCrossRefGoogle Scholar
  98. 98.
    Sarnowska E, Grzybowska EA, Sobczak K, Konopinski R, Wilczynska A, Szwarc M, Sarnowski TJ, Krzyzosiak WJ, Siedlecki JA (2007) Hairpin structure within the 3′UTR of DNA polymerase beta mRNA acts as a post-transcriptional regulatory element and interacts with Hax-1. Nucleic Acids Res 35:5499–5510PubMedCrossRefGoogle Scholar
  99. 99.
    Al-Maghrebi M, Brule H, Padkina M, Allen C, Holmes WM, Zehner ZE (2002) The 3′ untranslated region of human vimentin mRNA interacts with protein complexes containing eEF-1gamma and HAX-1. Nucleic Acids Res 30:5017–5028PubMedCrossRefGoogle Scholar
  100. 100.
    Lauriat TL, Dracheva S, Kremerskothen J, Duning K, Haroutunian V, Buxbaum JD, Hyde TM, Kleinman JE, Alison ML (2006) Characterization of KIAA0513, a novel signaling molecule that interacts with modulators of neuroplasticity, apoptosis, and the cytoskeleton. Brain Res 1121:1–11PubMedCrossRefGoogle Scholar
  101. 101.
    Mirmohammadsadegh A, Tartler U, Michel G, Baer A, Walz M, Wolf R, Ruzicka T, Hengge UR (2003) HAX-1, identified by differential display reverse transcription polymerase chain reaction, is overexpressed in lesional psoriasis. J Invest Dermatol 120:1045–1051PubMedCrossRefGoogle Scholar
  102. 102.
    Pizzo P, Pozzan T (2007) Mitochondria-endoplasmic reticulum choreography: structure and signaling dynamics. Trends Cell Biol 17:511–517PubMedCrossRefGoogle Scholar
  103. 103.
    Klein C, Grudzien M, Appaswamy G, Germeshausen M, Sandrock I, Schaffer AA, Rathinam C, Boztug K, Schwinzer B, Rezaei N, Bohn G, Melin M, Carlsson G, Fadeel B, Dahl N, Palmblad J, Henter JI, Zeidler C, Grimbacher B, Welte K (2007) HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease). Nat Genet 39:86–92PubMedCrossRefGoogle Scholar
  104. 104.
    Bohn G, Welte K, Klein C (2007) Severe congenital neutropenia: new genes explain an old disease. Curr Opin Rheumatol 19:644–650PubMedCrossRefGoogle Scholar
  105. 105.
    Matsubara K, Imai K, Okada S, Miki M, Ishikawa N, Tsumura M, Kato T, Ohara O, Nonoyama S, Kobayashi M (2007) Severe developmental delay and epilepsy in a Japanese patient with severe congenital neutropenia due to HAX1 deficiency. Haematologica 92:e123–e125PubMedCrossRefGoogle Scholar
  106. 106.
    Rezaei N, Moin M, Pourpak Z, Ramyar A, Izadyar M, Chavoshzadeh Z, Sherkat R, Aghamohammadi A, Yeganeh M, Mahmoudi M, Mahjoub F, Germeshausen M, Grudzien M, Horwitz MS, Klein C, Farhoudi A (2007) The clinical, immunohematological, and molecular study of Iranian patients with severe congenital neutropenia. J Clin Immunol 27:525–533PubMedCrossRefGoogle Scholar
  107. 107.
    Youle RJ, Strasser A (2008) The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9:47–59PubMedCrossRefGoogle Scholar
  108. 108.
    Annis MG, Yethon JA, Leber B, Andrews DW (2004) There is more to life and death than mitochondria: Bcl-2 proteins at the endoplasmic reticulum. Biochim Biophys Acta 1644:115–123PubMedCrossRefGoogle Scholar
  109. 109.
    Cory S, Adams JM (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2:647–656PubMedCrossRefGoogle Scholar
  110. 110.
    Demaurex N, Distelhorst C (2003) Cell biology. Apoptosis—the calcium connection. Science 300:65–67PubMedCrossRefGoogle Scholar
  111. 111.
    Pinton P, Ferrari D, Rapizzi E, Di Virgilio F, Pozzan T, Rizzuto R (2001) The Ca2+ concentration of the endoplasmic reticulum is a key determinant of ceramide-induced apoptosis: significance for the molecular mechanism of Bcl-2 action. Embo J 20:2690–2701PubMedCrossRefGoogle Scholar
  112. 112.
    Rizzuto R, Pinton P, Carrington W, Fay FS, Fogarty KE, Lifshitz LM, Tuft RA, Pozzan T (1998) Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science 280:1763–1766PubMedCrossRefGoogle Scholar
  113. 113.
    Szabadkai G, Rizzuto R (2004) Participation of endoplasmic reticulum and mitochondrial calcium handling in apoptosis: more than just neighborhood? FEBS Lett 567:111–115PubMedCrossRefGoogle Scholar
  114. 114.
    Franzini-Armstrong C (2007) ER-mitochondria communication. How privileged? Physiology (Bethesda) 22:261–268Google Scholar
  115. 115.
    Akao Y, Otsuki Y, Kataoka S, Ito Y, Tsujimoto Y (1994) Multiple subcellular localization of bcl-2: detection in nuclear outer membrane, endoplasmic reticulum membrane, and mitochondrial membranes. Cancer Res 54:2468–2471PubMedGoogle Scholar
  116. 116.
    Krajewski S, Tanaka S, Takayama S, Schibler MJ, Fenton W, Reed JC (1993) Investigation of the subcellular distribution of the bcl-2 oncoprotein: residence in the nuclear envelope, endoplasmic reticulum, and outer mitochondrial membranes. Cancer Res 53:4701–4714PubMedGoogle Scholar
  117. 117.
    Lithgow T, van Driel R, Bertram JF, Strasser A (1994) The protein product of the oncogene bcl-2 is a component of the nuclear envelope, the endoplasmic reticulum, and the outer mitochondrial membrane. Cell Growth Differ 5:411–417PubMedGoogle Scholar
  118. 118.
    Zong WX, Li C, Hatzivassiliou G, Lindsten T, Yu QC, Yuan J, Thompson CB (2003) Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis. J Cell Biol 162:59–69PubMedCrossRefGoogle Scholar
  119. 119.
    Nutt LK, Pataer A, Pahler J, Fang B, Roth J, McConkey DJ, Swisher SG (2002) Bax and Bak promote apoptosis by modulating endoplasmic reticular and mitochondrial Ca2+ stores. J Biol Chem 277:9219–9225PubMedCrossRefGoogle Scholar
  120. 120.
    Hsu YT, Wolter KG, Youle RJ (1997) Cytosol-to-membrane redistribution of Bax and Bcl-X(L) during apoptosis. Proc Natl Acad Sci USA 94:3668–3672PubMedCrossRefGoogle Scholar
  121. 121.
    Zhu W, Cowie A, Wasfy GW, Penn LZ, Leber B, Andrews DW (1996) Bcl-2 mutants with restricted subcellular location reveal spatially distinct pathways for apoptosis in different cell types. EMBO J 15:4130–4141PubMedGoogle Scholar
  122. 122.
    Rudner J, Lepple-Wienhues A, Budach W, Berschauer J, Friedrich B, Wesselborg S, Schulze-Osthoff K, Belka C (2001) Wild-type, mitochondrial and ER-restricted Bcl-2 inhibit DNA damage-induced apoptosis but do not affect death receptor-induced apoptosis. J Cell Sci 114:4161–4172PubMedGoogle Scholar
  123. 123.
    Hacki J, Egger L, Monney L, Conus S, Rosse T, Fellay I, Borner C (2000) Apoptotic crosstalk between the endoplasmic reticulum and mitochondria controlled by Bcl-2. Oncogene 19:2286–2295PubMedCrossRefGoogle Scholar
  124. 124.
    Annis MG, Zamzami N, Zhu W, Penn LZ, Kroemer G, Leber B, Andrews DW (2001) Endoplasmic reticulum localized Bcl-2 prevents apoptosis when redistribution of cytochrome c is a late event. Oncogene 20:1939–1952PubMedCrossRefGoogle Scholar
  125. 125.
    He H, Lam M, McCormick TS, Distelhorst CW (1997) Maintenance of calcium homeostasis in the endoplasmic reticulum by Bcl-2. J Cell Biol 138:1219–1228PubMedCrossRefGoogle Scholar
  126. 126.
    Pinton P, Ferrari D, Magalhaes P, Schulze-Osthoff K, Di Virgilio F, Pozzan T, Rizzuto R (2000) Reduced loading of intracellular Ca(2+) stores and downregulation of capacitative Ca(2+) influx in Bcl-2-overexpressing cells. J Cell Biol 148:857–862PubMedCrossRefGoogle Scholar
  127. 127.
    Vanden Abeele F, Skryma R, Shuba Y, Van Coppenolle F, Slomianny C, Roudbaraki M, Mauroy B, Wuytack F, Prevarskaya N (2002) Bcl-2-dependent modulation of Ca(2+) homeostasis and store-operated channels in prostate cancer cells. Cancer Cell 1:169–179PubMedCrossRefGoogle Scholar
  128. 128.
    Foyouzi-Youssefi R, Arnaudeau S, Borner C, Kelley WL, Tschopp J, Lew DP, Demaurex N, Krause KH (2000) Bcl-2 decreases the free Ca2+ concentration within the endoplasmic reticulum. Proc Natl Acad Sci USA 97:5723–5728PubMedCrossRefGoogle Scholar
  129. 129.
    Li C, Fox CJ, Master SR, Bindokas VP, Chodosh LA, Thompson CB (2002) Bcl-X(L) affects Ca(2+) homeostasis by altering expression of inositol 1,4,5-trisphosphate receptors. Proc Natl Acad Sci USA 99:9830–9835PubMedCrossRefGoogle Scholar
  130. 130.
    Li C, Wang X, Vais H, Thompson CB, Foskett JK, White C (2007) Apoptosis regulation by Bcl-x(L) modulation of mammalian inositol 1,4,5-trisphosphate receptor channel isoform gating. Proc Natl Acad Sci USA 104:12565–12570PubMedCrossRefGoogle Scholar
  131. 131.
    White C, Li C, Yang J, Petrenko NB, Madesh M, Thompson CB, Foskett JK (2005) The endoplasmic reticulum gateway to apoptosis by Bcl-X(L) modulation of the InsP3R. Nat Cell Biol 7:1021–1028PubMedCrossRefGoogle Scholar
  132. 132.
    Nutt LK, Chandra J, Pataer A, Fang B, Roth JA, Swisher SG, O'Neil RG, McConkey DJ (2002) Bax-mediated Ca2+ mobilization promotes cytochrome c release during apoptosis. J Biol Chem 277:20301–20308PubMedCrossRefGoogle Scholar
  133. 133.
    Scorrano L, Oakes SA, Opferman JT, Cheng EH, Sorcinelli MD, Pozzan T, Korsmeyer SJ (2003) BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science 300:135–139PubMedCrossRefGoogle Scholar
  134. 134.
    Oakes SA, Scorrano L, Opferman JT, Bassik MC, Nishino M, Pozzan T, Korsmeyer SJ (2005) Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum. Proc Natl Acad Sci USA 102:105–110PubMedCrossRefGoogle Scholar
  135. 135.
    Palmer AE, Jin C, Reed JC, Tsien RY (2004) Bcl-2-mediated alterations in endoplasmic reticulum Ca2+ analyzed with an improved genetically encoded fluorescent sensor. Proc Natl Acad Sci USA 101:17404–17409PubMedCrossRefGoogle Scholar
  136. 136.
    Chen R, Valencia I, Zhong F, McColl KS, Roderick HL, Bootman MD, Berridge MJ, Conway SJ, Holmes AB, Mignery GA, Velez P, Distelhorst CW (2004) Bcl-2 functionally interacts with inositol 1,4,5-trisphosphate receptors to regulate calcium release from the ER in response to inositol 1,4,5-trisphosphate. J Cell Biol 166:193–203PubMedCrossRefGoogle Scholar
  137. 137.
    Rong Y, Distelhorst CW (2008) Bcl-2 protein family members: versatile regulators of calcium signaling in cell survival and apoptosis. Annu Rev Physiol 70:73–91PubMedCrossRefGoogle Scholar
  138. 138.
    Dremina ES, Sharov VS, Schoneich C (2006) Displacement of SERCA from SR lipid caveolae-related domains by Bcl-2: a possible mechanism for SERCA inactivation. Biochemistry 45:175–184PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Elizabeth Vafiadaki
    • 1
  • Vasiliki Papalouka
    • 1
  • Demetrios A. Arvanitis
    • 1
  • Evangelia G. Kranias
    • 1
    • 2
  • Despina Sanoudou
    • 1
  1. 1.Molecular Biology DivisionBiomedical Research Foundation, Academy of AthensAthensGreece
  2. 2.Department of Pharmacology and Cell Biophysics, College of MedicineUniversity of CincinnatiCincinnatiUSA

Personalised recommendations