Calreticulin pp 133-141 | Cite as

ER Calcium and ER Chaperones: New Players in Apoptosis?

  • Nicolas Demaurex
  • Maud Frieden
  • Serge Arnaudeau
Chapter
Part of the Molecular Biology Intelligence Unit book series (MBIU)

Abstract

By using calcium ions as an intracellular messenger, cells walk a tight rope between life and death. Because critical cellular functions depend on the precise delivery of Ca2+ at the right time and place, calcium ions must navigate at all times between intracellular calcium stores and target proteins located in the cytosol, the mitochondria, or the nucleus. Due to the toxicity of high Ca2+ concentrations, even slight disruption of the elaborate calcium signaling machinery can have devastating consequences on cell functions: too much or too little calcium at the wrong time and place might lead to rapid cell death by necrosis, or to the induction of the cell death program of apoptosis. ER chaperones, and most notably calreticulin, play a key role in the making and decoding of both normal and pathological calcium signals. Calreticulin is the main Ca2+-binding protein residing in the ER, and as such contributes most of the ER Ca2+ buffering capacity. Calreticulin also acts as a chaperone for several ER Ca2+ transport proteins, and thus indirectly modulates Ca2+ fluxes across the ER membrane. Accordingly, over- or underexpression of calreticulin leads to rapid and severe alterations in ER Ca2+ homeostasis. Calreticulin expression levels are controlled by the ER Ca2+ levels, thus enabling cells to mount an appropriate response during long-term perturbations in ER Ca2+ storage. However, calreticulin levels are also increased by a variety of cellular stress conditions, and this upregulation might contribute to the Ca2+ signaling defects leading to apoptosis. In this chapter, we will review the role of calreticulin and of other ER chaperones in the control of Ca2+ -mediated apoptosis.

Keywords

Unfold Protein Response Ryanodine Receptor ofER Calcium SERCA Inhibitor Unfold Protein Response Element 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972; 26(4):239–57.PubMedCrossRefGoogle Scholar
  2. 2.
    Juin P, Pelletier M, Oliver L et al. Induction of a caspase-3-like activity by calcium in normal cytosolic extracts triggers nuclear apoptosis in a cell-free system. J Biol Chem 1998; 273(28):17559–64.PubMedCrossRefGoogle Scholar
  3. 3.
    Kaiser N, Edelman IS. Calcium dependence of glucocorticoid-induced fymphocytolysis. Proc Natl Acad Sci USA 1977; 74(2):638–42.PubMedCrossRefGoogle Scholar
  4. 4.
    Kaiser N, Edelman IS. Further studies on the role of calcium in glucocorticoid-induced lymphocytolysis. Endocrinology 1978; 103(3):936–42.PubMedCrossRefGoogle Scholar
  5. 5.
    Kaiser N, Edelman IS. Calcium dependence of ionophore A23187-induced lymphocyte cytotoxicity. Cancer Res 1978; 38(11Pt l):3599–603.PubMedGoogle Scholar
  6. 6.
    Dowd DR, MacDonald PN, Komm BS et al. Stable expression of the calbindin-D28K complementary DNA interferes with the apoptotic pathway in lymphocytes. Mol Endocrinol 1992; 6(11):1843–8.PubMedCrossRefGoogle Scholar
  7. 7.
    McConkey DJ, Hartzeil P, Nicotera P et al. Calcium-activated DNA fragmentation kills immature thymocytes. Faseb J 1989; 3(7):1843–9.PubMedGoogle Scholar
  8. 8.
    Aw TY, Nicotera P, Manzo L et al. Tributyltin stimulates apoptosis in rat thymocytes. Arch Biochem Biophys 1990; 283(1):46–50.PubMedCrossRefGoogle Scholar
  9. 9.
    McConkey DJ, Chow SC, Orrenius S et al. NK cell-induced cytotoxicity is dependent on a Ca2+ increase in the target. Faseb J 1990; 4(9):2661–4.PubMedGoogle Scholar
  10. 10.
    Juntti-Berggren L, Larsson O, Rorsman P et al. Increased activity of L-type Ca2+ channels exposed to serum from patients with type I diabetes. Science 1993; 261(5117):86–90.PubMedCrossRefGoogle Scholar
  11. 11.
    Jiang S, Chow SC, Nicotera P et al. Intraceîlular Ca2+ signals activate apoptosis in thymocytes; studies using the Ca(2+)-ATPase inhibitor thapsigargin. Exp Cell Res 1994; 212(1):84–92.PubMedCrossRefGoogle Scholar
  12. 12.
    Kaneko Y, Tsukamoto A. Thapsigargin-induced persistent intracellular calcium pool depletion and apoptosis in human hepatoma cells. Cancer Lett 1994; 79(2):147–55.PubMedCrossRefGoogle Scholar
  13. 13.
    Levick V, Coffey H, D’Mello SR. Opposing effects of thapsigargin on the survival of developing cerebellar granule neurons in culture. Brain Res 1995; 676(2):325–35.PubMedCrossRefGoogle Scholar
  14. 14.
    Koike T, Martin DP, Johnson EM Jr. Role of Ca2+ channels in the ability of membrane depolarization to prevent neuronal death induced by trophic-factor deprivation: evidence that levels of internal Ca2+ determine nerve growth factor dependence of sympathetic ganglion cells. Proc Natl Acad Sci USA 1989; 86(16):6421–5.PubMedCrossRefGoogle Scholar
  15. 15.
    Yano S, Tokumitsu H, Soderling TR. Calcium promotes cell survival through CaM-K kinase activation of the protein-kinase-B pathway. Nature 1998; 396(6711):584–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Berridge MJ, Lipp P, Bootman MD. The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 2000; 1(1):11–21.PubMedCrossRefGoogle Scholar
  17. 17.
    Rizzuto R, Brini M, Murgia M et al. Microdomains with high Ca2+ close to IP3-sensitive channels that are sensed by neighboring mitochondria. Science 1993; 262(5134):744–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Szalai G, Csordas G, Hantash BM et al. Calcium signal transmission between ryanodine receptors and mitochondria. J Biol Chem 2000; 275(20):15305–13.PubMedCrossRefGoogle Scholar
  19. 19.
    Pacher P, Thomas AP, Hajnoczky G. Ca2+ marks: miniature calcium signals in single mitochondria driven by ryanodine receptors. Proc Natl Acad Sci USA 2002; 99(4):2380–5.PubMedCrossRefGoogle Scholar
  20. 20.
    Montero M, Alonso MT, Carnicero E et al. Chromaffin-cell stimulation triggers fast millimolar mitochondrial Ca2+ transients that modulate secretion. Nat Cell Biol 2000; 2(2):57–61.PubMedCrossRefGoogle Scholar
  21. 21.
    Arnaudeau S, Kelley WL, Walsh JV Jr. et al. Mitochondria recycle Ca(2+) to the endoplasmic reticulum and prevent the depletion of neighboring endoplasmic reticulum regions. J Biol Chem 2001; 276(31):29430–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Kroemer G. The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nat Med 1997; 3(6):614–20.PubMedCrossRefGoogle Scholar
  23. 23.
    Liu X, Kim CN, Yang J et al. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 1996; 86(1):147–57.PubMedCrossRefGoogle Scholar
  24. 24.
    Kluck RM, Bossy-Wetzel E, Green DR et al. The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 1997; 275(5303):1132–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Mancini M, Nicholson DW, Roy S et al. The caspase-3 precursor has a cytosolic and mitochondrial distribution: implications for apoptotic signaling. J Cell Biol 1998; 140(6):1485–95.PubMedCrossRefGoogle Scholar
  26. 26.
    Susin SA, Lorenzo HK, Zamzami N et al. Mitochondrial release of caspase-2 and-9 during the apoptotic process. J Exp Med 1999; 189(2):381–94.PubMedCrossRefGoogle Scholar
  27. 27.
    Susin SA, Lorenzo HK, Zamzami N et al. Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 1999; 397(6718):441–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Du C, Fang M, Li Y et al. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 2000; 102(1):33–42.PubMedCrossRefGoogle Scholar
  29. 29.
    Verhagen AM, Ekert PG, Pakusch M et al. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 2000; 102(1):43–53.PubMedCrossRefGoogle Scholar
  30. 30.
    Rizzuto R, Pinton P, Carrington W et al. Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science 1998; 280(5370):1763–6.PubMedCrossRefGoogle Scholar
  31. 31.
    Khan AA, Soloski MJ, Sharp AH et al. Lymphocyte apoptosis: mediation by increased type 3 inositol 1,4,5-trisphosphate receptor. Science 1996; 273(5274):503–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Blackshaw S, Sawa A, Sharp AH et al. Type 3 inositol 1,4,5-trisphosphate receptor modulates cell death. Faseb J 2000; 14(10):1375–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Wang HG, Pathan N, Ethell IM et al. Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD. Science 1999; 284(5412):339–43.PubMedCrossRefGoogle Scholar
  34. 34.
    Jayaraman T, Marks AR. Calcineurin is downstream of the inositol 1,4,5-trisphosphate receptor in the apoptotic and cell growth pathways. J Biol Chem 2000; 275(9):6417–20.PubMedCrossRefGoogle Scholar
  35. 35.
    Pinton P, Ferrari D, Rapizzi E et al. 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 2001; 20(ll):2690–701.PubMedCrossRefGoogle Scholar
  36. 36.
    Nakamura K, Zuppini A, Arnaudeau S et al. Functional specialization of calreticulin domains. J Cell Biol 2001; 154(5):961–72.PubMedCrossRefGoogle Scholar
  37. 37.
    Nakamura K, Bossy-Wetzel E, Burns K et al. Changes in endoplasmic reticulum luminal environment affect cell sensitivity to apoptosis. J Cell Biol 2000; 150(4):731–40.PubMedCrossRefGoogle Scholar
  38. 38.
    Szalai G, Krishnamurthy R, Hajnoczky G. Apoptosis driven by IP(3)-linked mitochondrial calcium signals. Embo J 1999; 18(22):6349–61.PubMedCrossRefGoogle Scholar
  39. 39.
    Hajnoczky G, Csordas G, Madesh M et al. Control of apoptosis by IP(3) and ryanodine receptor driven calcium signals. Cell Calcium 2000; 28(5-6):349–63.CrossRefGoogle Scholar
  40. 40.
    Li P, Nijhawan D, Budihardjo I et al. Cytochrome c and dATP-dependent formation of Apaf-1/ caspase-9 complex initiates an apoptotic protease cascade. Cell 1997; 91(4):479–89.PubMedCrossRefGoogle Scholar
  41. 41.
    Zou H, Li Y, Liu X et al. An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem 1999; 274(17):11549–56.PubMedCrossRefGoogle Scholar
  42. 42.
    Krajewski S, Tanaka S, Takayama S et al. Investigation of the subcellular distribution of the bcl-2 oncoprotein: residence in the nuclear envelope, endoplasmic reticulum, and outer mitochondrial membranes. Cancer Res 1993; 53(19):4701–14.PubMedGoogle Scholar
  43. 43.
    Pinton P, Ferrari D, Magalhaes P et al. Reduced loading of intracellular Ca(2+) stores and downregulation of capacitative Ca(2+) influx in BcI-2-overexpressing cells. J Cell Biol 2000; 148(5):857–62.PubMedCrossRefGoogle Scholar
  44. 44.
    Foyouzi-Youssefi R, Arnaudeau S, Borner C et al. Bcl-2 decreases the free Ca2+ concentration within the endoplasmic reticulum. Proc Natl Acad Sci USA 2000; 97(11):5723–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Muchmore SW, Sattler M, Liang H et al. X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature 1996; 381(6580):335–41.PubMedCrossRefGoogle Scholar
  46. 46.
    Schendel SL, Montai M, Reed JC. Bcl-2 family proteins as ion-channels. Cell Death Differ 1998; 5(5):372–80.PubMedCrossRefGoogle Scholar
  47. 47.
    Schendel SL, Xie Z, Montai MO et al. Channel formation by antiapoptotic protein Bcl-2. Proc Natl Acad Sci USA 1997; 94(10):5113–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Schlesinger PH, Gross A, Yin XM et al. Comparison of the ion channel characteristics of proapoptotic BAX and antiapoptotic BCL-2. Proc Natl Acad Sci USA 1997; 94(21):11357–62.PubMedCrossRefGoogle Scholar
  49. 49.
    Welihinda AA, Tirasophon W, Kaufman RJ. The cellular response to protein misfolding in the endoplasmic reticulum. Gene Expr 1999; 7(4-6):293–300.PubMedGoogle Scholar
  50. 50.
    Nakagawa T, Zhu H, Morishima N et al. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 2000; 403(6765):98–103.PubMedCrossRefGoogle Scholar
  51. 51.
    Kaufman RJ. Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev 1999; 13(10):1211–33.PubMedCrossRefGoogle Scholar
  52. 52.
    Patil C, Walter P. Intracellular signaling from the endoplasmic reticulum to the nucleus: the unfolded protein response in yeast and mammals. Curr Opin Cell Biol 2001; 13(3):349–55.PubMedCrossRefGoogle Scholar
  53. 53.
    Vassilakos A, Michalak M, Lehrman MA et al. Oligosaccharide binding characteristics of the molecular chaperones calnexin and calreticulin. Biochemistry 1998; 37(10):3480–90.PubMedCrossRefGoogle Scholar
  54. 54.
    Ivessa NE, De Lemos-Chiarandini C, Gravotta D et al. The Brefeldin A-induced retrograde transport from the Golgi apparatus to the endoplasmic reticulum depends on calcium sequestered to intracellular stores. J Biol Chem 1995; 270(43):25960–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Corbett EF, Oikawa K, Francois P et al. Ca2+ regulation of interactions between endoplasmic reticulum chaperones. J Biol Chem 1999; 274(10):6203–11.PubMedCrossRefGoogle Scholar
  56. 56.
    Bertolotti A, Zhang Y, Hendershor LM et al. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol 2000; 2(6):326–32.PubMedCrossRefGoogle Scholar
  57. 57.
    Yoshida H, Haze K, Yanagi H et al. Identification of the cis-acting endoplasmic reticulum stress response element responsible for transcriptional induction of mammalian glucose-regulated proteins. Involvement of basic leucine zipper transcription factors. J Biol Chem 1998; 273(50):33741–9.PubMedCrossRefGoogle Scholar
  58. 58.
    Lee AS. Mammalian stress response: induction of the glucose-regulated protein family. Curr Opin Cell Biol 1992; 4(2):267–73.PubMedCrossRefGoogle Scholar
  59. 59.
    Kozutsumi Y, Segal M, Normington K et al. The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins. Nature 1988; 332(6163):462–4.PubMedCrossRefGoogle Scholar
  60. 60.
    Lee AS. The glucose-regulated proteins: stress induction and clinical applications. Trends Biochem Sci 2001; 26(8):504–10.PubMedCrossRefGoogle Scholar
  61. 61.
    Caspersen C, Pedersen PS, Treiman M. The sarco/endoplasmic reticulum calcium-ATPase 2b is an endoplasmic reticulum stress-inducible protein. J Biol Chem 2000; 275(29):22363–72.PubMedCrossRefGoogle Scholar
  62. 62.
    McCormick TS, McColl KS, Distelhorst CW. Mouse lymphoma cells destined to undergo apoptosis in response to thapsigargin treatment fail to generate a calcium-mediated grp78/grp94 stress response. J Biol Chem 1997; 272(9):6087–92.PubMedCrossRefGoogle Scholar
  63. 63.
    Miyake H, Hara I, Arakawa S et al. Stress protein GRP78 prevents apoptosis induced by calcium îonophore, ionomycin, but not by glycosylation inhibitor, tunicamycin, in human prostate cancer cells. J Cell Biochem 2000; 77(3):396–408.PubMedCrossRefGoogle Scholar
  64. 64.
    Harding HP, Zhang Y, Ron D. Protein translation and folding are coupled by an endoplasmicreticulum-resident kinase. Nature 1999; 397(6716):271–4.PubMedCrossRefGoogle Scholar
  65. 65.
    Shi Y, Vattem KM, Sood R et al. Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control. Mol Cell Biol 1998; 18(12):7499–509.PubMedGoogle Scholar
  66. 66.
    Harding HP, Zhang Y, Bertolotti A et al. Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol Cell 2000; 5(5):897–904.PubMedCrossRefGoogle Scholar
  67. 67.
    Nakagawa T, Yuan J. Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis. J Cell Biol 2000; 150(4):887–94.PubMedCrossRefGoogle Scholar
  68. 68.
    Fujita N, Nagahashi A, Nagashima K et al. Acceleration of apoptotic cell death after the cleavage of Bcl-XL protein by caspase-3-like proteases. Oncogene 1998; 17(10):1295–304.PubMedCrossRefGoogle Scholar
  69. 69.
    Clem RJ, Cheng EH, Karp CL et al. Modulation of cell death by Bcl-XL through caspase interaction. Proc Natl Acad Sci USA 1998; 95(2):554–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Reddy RK, Lu J, Lee AS. The endoplasmic reticulum chaperone glycoprotein GRP94 with Ca(2+)-binding and antiapoptotic properties is a novel proteolytic target of calpain during etoposide-induced apoptosis. J Biol Chem 1999; 274(40):28476–83.PubMedCrossRefGoogle Scholar
  71. 71.
    Yoneda T, Imaizumi K, Oono K et al. Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. J Biol Chem 2001; 276(17):13935–40.PubMedGoogle Scholar
  72. 72.
    McCullough KD, Martindale JL, Klotz LO et al. Gaddl53 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. Mol Cell Biol 2001; 21(4):1249–59.PubMedCrossRefGoogle Scholar
  73. 73.
    Kawahara K, Oyadomari S, Gotoh T et al. Induction of CHOP and apoptosis by nitric oxide in p53-deficient microglial cells. FEBS Lett 2001; 506(2):135–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Nicolas Demaurex
  • Maud Frieden
  • Serge Arnaudeau

There are no affiliations available

Personalised recommendations