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Cell Signaling in Vascular Inflammation pp 155–165Cite as

Plasma Membrane-to-Nucleus Calcium Signaling

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Abstract

Calcium is a ubiquitous cellular second messenger that mediates a vast array of cellular processes. Elevation of intracellular calcium activates signaling cascades that are able to target the nucleus, where they modify gene transcription. The eukaryotic cell is wired up in a sophisticated manner to enable it to respond differently to different calcium signals. In this way a single second messenger can exert differing effects within the same cell.

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References

  1. Carafoli, E. and Penniston, J. (1985) The calcium signal. Sci. Am. 253, 50–58.

    Article  Google Scholar 

  2. Verkhratsky, A. J. and Petersen, O. H. (1998) Neuronal calcium stores. Cell Calcium 24, 333–343.

    Article  CAS  PubMed  Google Scholar 

  3. Bliss, T. V. P. and Collingridge, G. L. (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31–38.

    Article  CAS  PubMed  Google Scholar 

  4. Robertson, E. D., English, J. D., and Sweatt, J. D. (1996) A biochemists view of LTP. Learning and Memory 3, 1–24.

    Article  Google Scholar 

  5. Malinow, R., Mainen, Z. F., and Hayashi, Y. (2000) LTP mechanisms: from silence to four-lane traffic. Curr. Opin. Neurobiol. 10, 352–357.

    Article  CAS  PubMed  Google Scholar 

  6. Bading, H., Ginty, D. D., and Greenberg, M. E. (1993) Regulation of gene expression in hippocampal neurons by distinct calcium signaling pathways. Science 260, 181–186.

    Article  CAS  PubMed  Google Scholar 

  7. Milner, B., Corkin, S., and Teurber, H. (1968) Further analysis of the hippocampal amnesic syndrome: 14 year follow-up study of H.M. Neurophysiologia 6, 215–234.

    Google Scholar 

  8. Nadel, L. and Moscovitch, M. (1997) Memory consolidation, retrograde amnesia and the hippocampal complex. Curr. Opin. Neurobiol. 7, 217–227.

    Article  CAS  PubMed  Google Scholar 

  9. Bliss, T. V. P. and Lomo, T. (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaes-thetized rabbit following stimulation of the perforant path. J. Physiol. 232, 331–356.

    CAS  PubMed  Google Scholar 

  10. Frey, U., Huang, Y-Y., and Kandel, E. R. (1993) Effects of cAMP simulate a late stage of LTP in hippocampal CAL Neurons. Science 260, 1661–1664.

    Article  CAS  PubMed  Google Scholar 

  11. Nguyen, P. V., Abel, T., and Kandel, E. R. (1994) Requirement of a critical period of transcription for induction of a late phase of LTP. Science 265, 1104–1107.

    Article  CAS  PubMed  Google Scholar 

  12. Lynch, G., Larson, J., Kelso, S., Barrionuevo, G., and Schottler, F. (1983) Intracellular injections of EGTA block induction of hippocampal long-term potentiation. Nature 305, 719–721.

    Article  CAS  PubMed  Google Scholar 

  13. Ptashne, M. and Gann, A. (1997) Transcriptional activation by recruitment. Nature 386, 569–577.

    Article  CAS  PubMed  Google Scholar 

  14. Whitmarsh, A. J. and Davis, R. (2000) Regulation of transcription factor function by phosphorylation. Cell. Mol. Life Sci. 57, 1172–1183.

    Article  CAS  PubMed  Google Scholar 

  15. Montminy, M. R., Sevarino, K. A., Wagner, J. A., Mandel, G., and Goodman, R. H. (1986) Identification of a cyclic-AMP-responsive element within the rat somatostatin gene. Proc. Natl. Acad. Sci. USA 83, 6682–6686.

    Article  CAS  PubMed  Google Scholar 

  16. Comb, M., Birnberg, N. C., Seasholtz, A., Herbert, E., and Goodman, H. M. (1986) A cyclic AMP and phorbol ester-inducible DNA element. Nature 323, 353–356.

    Article  CAS  PubMed  Google Scholar 

  17. Hardingham, G. E., Fukunaga, Y., and Bading, H. (2002) Extrasynaptic NMDARs oppose synaptic NMDARs by trig-gering CREB shut-off and cell death pathways. Nat. Neurosci. 5, 405–414.

    CAS  PubMed  Google Scholar 

  18. Impey, S., Mark, M., Villacres, E. C., Poser, S., Chavkin, C., and Storm, D. R. (1996) Induction of CRE-medaited gene expression by stimuli that generate long-lasting LTP in Area CA1 of the hippocampus. Neuron 16, 973–982.

    Article  CAS  PubMed  Google Scholar 

  19. Montminy, M. R., and Bilezikjian, L. M. Binding ofa nuclear protein to the cyclic-AMP response element of the soma-tostatin gene. Nature (1987) 328, 175–178.

    Article  CAS  PubMed  Google Scholar 

  20. Treisman, R. (1985) Transient accumulation of c-fos RNA following serum stimulation requires a conserved 5′ element and c-fos 3′ sequences. bdCell 42, 889–902.

    CAS  Google Scholar 

  21. Treisman, R. (1987) Identification and purification of a polypeptide that binds to the c-fos serum response element. EMBO J. 6, 2711–2717.

    CAS  PubMed  Google Scholar 

  22. Schröter, H., Shaw, P. E., and Nordheim, A. (1987) Purification of intercalator-released p67, a polypeptide that inter-acts specifically with the c-fos serum response element. Nucleic Acids Res. 15, 10,145–10,157.

    Article  PubMed  Google Scholar 

  23. Hardingham, G. E., Arnold, F., and Bading, H. (2001) Calcium microdomain near NMDA receptors: on-switch of ERK-dependent synapse-to-nucleus communication. Nat. Neurosci. 4, 565–566.

    Article  CAS  PubMed  Google Scholar 

  24. Rao, A., Luo, C., and Hogan, P. G. (1997) Transcription factors of the NFAT family: regulation and function. Annu. Rev. Immunol. 15, 707–47.

    Article  CAS  PubMed  Google Scholar 

  25. Graef, I. A., Mermelstein, P. G., Stankunas, K., et al. (1999) L-type calcium channels and GSK-3 regulate the activity of NF-ATc4 in hippocampal neurons. Nature 401, 703–708.

    Article  CAS  PubMed  Google Scholar 

  26. Silva, A. J., Kogan, J. H., Frankland, P. W., and Kida, S. (1998) CREB and memory. Annu. Rev. Neurosci. 21, 127–148.

    Article  CAS  PubMed  Google Scholar 

  27. Guzowski, G. A. and McGaugh, J. L. (1997) Antisense oligodeoxynucleotide-mediated disruption of hippocampal CREB protein levels impairs memory of a spatial task. Proc. Natl. Acad. Sci. USA 94, 2693–98.

    Article  CAS  PubMed  Google Scholar 

  28. Bourtchuladze, R., Frenguelli, B., Blendy, J., Cioffi, D., Schutz, G., and Silva, A. J. (1994) Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79, 59–68.

    Article  CAS  PubMed  Google Scholar 

  29. Blendy, J. A. and Maldonado, R. (1998) Genetic analysis of drug addiction: the role of cAMP response element binding protein. J. Mol. Med. 76, 104–110.

    Article  CAS  PubMed  Google Scholar 

  30. King, D. P. and Takahashi, J. S. (2000) Molecular genetics of circadian rhythms in mammals. Annu. Rev. Neurosci. 23, 713–742.

    Article  CAS  PubMed  Google Scholar 

  31. Walton, M. R. and Dragunow, M. (2000) Is CREB a key to neuronal survival? Trends Neurosci. 23, 48–53.

    Article  CAS  PubMed  Google Scholar 

  32. Lonze, B. E., Riccio, A., Cohen, S., and Ginty, D. D. (2002) Apoptosis, axonal growth defects, and degeneration of peripheral neurons in mice lacking CREB. Neuron 34, 371–385.

    Article  CAS  PubMed  Google Scholar 

  33. Shieh, P. B., Hu, S-C., Bobb, K., Timmusk, T., and Ghosh, A. (1998) Identification of a signaling pathway involved in calcium regulation of BDNF expression. Neuron 20, 727–740.

    Article  CAS  PubMed  Google Scholar 

  34. Tao, X., Finkbeiner, S., Arnold, D. B., Shaywitz, A. J., and Greenberg, M. E. (1988) Calcium influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron 20, 709–726.

    Article  Google Scholar 

  35. Ghosh, A., Carnahan, J., and Greenberg, M. E. (1994) Requirement for BDNF in activity-dependent survival of cortical neurons. Science 263, 1618–1623.

    Article  CAS  PubMed  Google Scholar 

  36. Schwartz, P. M., Borghesani, P. R., Levy, R. L., Pomeroy, S. L., and Segal, R. A. (1997) Abnormal cerebellar develop-ment and foliation in BDNF-/-mice reveals a role for neurotrophins in CNS patterning. Neuron 19, 269–281.

    Article  CAS  PubMed  Google Scholar 

  37. Sasaki, M., Gonzalez-Zulueta, M., Huang, H., et al. (2000) Dynamic regulation of neuronal NO synthase transcription by calcium influx through a CREB family transcription factor-dependent mechanism. Proc. Natl. Acad. Sci. USA 97, 8617–8622.

    Article  CAS  PubMed  Google Scholar 

  38. Baranes, D., Lederfein, D., Huang, Y. Y., Chen, M., Bailey, C. H., and Kandel, E. R. (1998) Tissue plasminogen activator contributes to the late phase of LTP and to synaptic growth in the hippocampal mossy fiber pathway. Neuron 21, 813–825.

    Article  CAS  PubMed  Google Scholar 

  39. Sheng, M., McFadden, G., and Greenberg, M. E. (1990) Membrane depolarization and calcium induce c-fos transcrip-tion via phosphorylation of transcription factor CREB. Neuron 4, 571–582.

    Article  CAS  PubMed  Google Scholar 

  40. Gonzalez, G. A. and Montminy, M. R. (1989) Cyclic AMP stimulates somatostatin gene transcription by phosphoryla-tion of CREB at serine 133. Cell 59, 675–680.

    Article  CAS  PubMed  Google Scholar 

  41. Sheng, M., Thompson, M. A., and Greenberg, M. E. (1991) CREB: a Ca2+-regulated transcription factor phosphory-lated by calmodulin-dependent kinases. Science 252, 1427–1430.

    Article  CAS  PubMed  Google Scholar 

  42. Ginty, D. D., Kornhauser, J. M., Thompson, M. A., et al. (1993) Regulation of CREB phosphorylation in the suprachiasmatic nucleus by light and a circadian clock. Science 260, 238–241.

    Article  CAS  PubMed  Google Scholar 

  43. Bito, H., Deisseroth, K., and Tsien, R. W. (1996) CREB phosphorylation and dephosphorylation: a calcium and stimu-lus dependent switch for hippocampal gene expression. Cell 87, 1203–1214.

    Article  CAS  PubMed  Google Scholar 

  44. West, A. E., Chen, W. G., Dalva, M. B., et al. (2001) Calcium regulation of neuronal gene expression. Proc. Natl. Acad. Sci. USA 98, 11024–31.

    Article  CAS  PubMed  Google Scholar 

  45. Sun, P., Enslen, H., Myung, P. S., and Maurer, R. A. (1994) Differential activation of CREB by Ca2+/-calmodulin-dependent protein kinases type II and type IV involves phosphorylation of a site that negatively regulates activity. Genes Dev. 8, 2527–2539.

    Article  CAS  PubMed  Google Scholar 

  46. Matthews, R. P., Guthrie, C. R., Wailes, L. M., Zhao, X., Means, A. R., and McKnight, G. S. (1994) Calcium/ calmodulin-dependent protein kinase types II and IV differentially regulate CREB-dependent gene expression. Mol. Cell. Biol. 14, 6107–6116.

    CAS  PubMed  Google Scholar 

  47. Heist, E. and Schulman, H. (1998) The role of Ca2+/calmodulin dependent protein kinases within the nucleus. Cell Calcium 23, 103–114.

    Article  CAS  PubMed  Google Scholar 

  48. Hook, S. S. and Means, A. R. (2001) Ca2+/CaM-dependent kinases: From activation to function. Annu. Rev. Pharmacol. Toxicol. 41, 471–505.

    Article  CAS  PubMed  Google Scholar 

  49. Soderling, T. R. and Stull, J. T. (2001) Structure and regulation of calcium/calmodulin-dependent protein kinases. Chem. Rev. 101, 2341–2351.

    Article  CAS  PubMed  Google Scholar 

  50. Kang, H., Sun, L. D., Atkins, C. M., Soderling, T. R., Wilson, M. A., and Tonegawa, S. (2001) An important role of neural activity-dependent CaMKIV signaling in the consolidation of long-term memory. Cell 106, 771–783.

    Article  CAS  PubMed  Google Scholar 

  51. Ho, N., Liauw, J. A., Blaeser, F. W., et al. (2000) Impaired synaptic plasticity and cAMP response element-binding protein activation in Ca2+/calmodulin-dependent protein kinase type IV/Gr-deficient mice. J. Neurosci. 20, 6459–6472.

    CAS  PubMed  Google Scholar 

  52. Ribar, T. J., Rodriguiz, R. M., Khiroug, L., Wetsel, W. C., Augustine, G. J., and Means, A. R. (2000) Cerebellar defects in Ca2+/calmodulin kinase IV-deficient mice. J. Neurosci. 20, RC107.

    CAS  PubMed  Google Scholar 

  53. Ginty, D. D., Bonni, A., and Greenberg, M. E. (1994) Nerve growth factor activates a Ras-dependent protein kinase that stimulates c-fos transcription via phosphorylation of CREB. Cell 77, 713–725.

    Article  PubMed  Google Scholar 

  54. Bonni, A., Ginty, D. D., Dudek, H., and Greenberg, M. E. (1995) Serine 133-phosphorylated CREB induces transcrip-tion via a cooperative mechanism that may confer specificity to neurotrophin signals. Mol. Cell. Neurosci. 6, 168–183.

    Article  CAS  PubMed  Google Scholar 

  55. Bading, H. and Greenberg, M. E. (1991) Stimulation of protein tyrosine phosphorylation by NMDA receptor activa-tion. Science 253, 912–914.

    Article  CAS  PubMed  Google Scholar 

  56. Adams, J. P. and Sweatt, J. D. (2002) Molecular psychology: Roles for the ERK MAP kinase cascade in memory. Annu. Rev. Pharmacol. Toxicol. 42, 135–163.

    Article  CAS  PubMed  Google Scholar 

  57. Hardingham, G. E., Chawla, S., Cruzalegui, F. H., and Bading, H. (1999) Control of recruitment and transcription-activating function of CBP determines gene regulation by NMDA receptors and L-type calcium channels. Neuron 22, 789–798.

    Article  CAS  PubMed  Google Scholar 

  58. Wu, G. Y., Deisseroth, K., and Tsien, R. W. (2001) Activity-dependent CREB phosphorylation: convergence of a fast, sensitive calmodulin kinase pathway and a slow, less sensitive mitogen-activated protein kinase pathway. Proc. Natl. Acad. Sci. USA 98, 2808–2813.

    Article  CAS  PubMed  Google Scholar 

  59. Impey, S. and Goodman, R. H. (2001) CREB signaling-timing is everything. Science-STKE PE1.

    Google Scholar 

  60. Xing, J., Ginty, D. D., and Greenberg, M. E. (1996) Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase. Science 273, 959–963.

    Article  CAS  PubMed  Google Scholar 

  61. Chawla, S., Hardingham, G. E., Quinn, D. R., and Bading, H. (1998) CBP: a signal-regulated transcriptional coactivator controlled by nuclear calcium and CaM kinase IV. Science 281, 1505–1509.

    Article  CAS  PubMed  Google Scholar 

  62. Chrivia, J. C., Kwok, R. P. S., Lamb, N., Hagiwara, M., Montminy, M. R., Goodman, R. H. (1993) Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 365, 855–859.

    Article  CAS  PubMed  Google Scholar 

  63. Goldman, P. S., Tran, V. K., and Goodman, R. H. (1997) The multifunctional role of the co-activator CBP in transcrip-tional regulation. Recent Prog. Horm. Res. 52, 103–120.

    CAS  PubMed  Google Scholar 

  64. Hu, S. C., Chrivia, J., and Ghosh, A. (1999) Regulation of CBP-mediated transcription by neuronal calcium signaling. Neuron 22, 799–808.

    Article  CAS  PubMed  Google Scholar 

  65. Impey, S., Fong, A. L., Wang, Y., et al. (2002) Phosphorylation of CBP mediates transcriptional activation by neural activity and CaM kinase IV. Neuron 34, 235–244.

    Article  CAS  PubMed  Google Scholar 

  66. Cruzalegui, F. H., Hardingham, G., and Bading, H. (1999) Jun functions as a calcium-regulated transcriptional acti-vator in the absence of JNK/SAPK1 activation. EMBO J. 18, 1335–1344.

    Article  CAS  PubMed  Google Scholar 

  67. Hardingham, G. E., Chawla, S., Johnson, C. M., and Bading, H. (1997) Distinct functions of nuclear and cytoplasmic calcium in the control of gene expression. Nature 385, 260–265.

    Article  CAS  PubMed  Google Scholar 

  68. Hardingham, G. E., Arnold, F. A., and Bading, H. (2001) Nuclear calcium signaling controls CREB-mediated gene expression triggered by synaptic activity. Nat. Neurosci. 4, 261–267.

    Article  CAS  PubMed  Google Scholar 

  69. Hardingham, G. E. and Bading, H. (1998) Nuclear calcium: a key regulator of gene expression. Biometals 11, 345–358.

    Article  CAS  PubMed  Google Scholar 

  70. Sala, C., Rudolph-Correia, S., and Sheng, M. (2000) Developmentally regulated NMDA receptor-dependent dephos-phorylation of cAMP response element-binding protein (CREB) in hippocampal neurons. J. Neurosci. 20, 3529–3536.

    CAS  PubMed  Google Scholar 

  71. Deisseroth, K., Heist, E. K., and Tsien, R. W. (1998) Translocation of calmodulin to the nucleus supports CREB phosphorylation in hippocampal neurons. Nature 392, 198–202.

    Article  CAS  PubMed  Google Scholar 

  72. Husi, H., Ward, M. A., Choudhary, J. A., Blackstock, W. P., and Grant, S. G. N. (2000) Proteomic analysis of NMDA receptor-adhesion protein signaling complexes. Nat. Neurosci. 3, 661–669.

    Article  CAS  PubMed  Google Scholar 

  73. Emptage, N., Bliss, T. V. P., and Fine, A. (1999) Single synaptic events evoke NMDA receptor-mediated release of calcium from internal stores in hippocampal dendritic spines. Neuron 22, 115–124.

    Article  CAS  PubMed  Google Scholar 

  74. Alford, S., Frenguelli, B. G., Schofield, J. G., and Collingridge, G. L. (1993) Characterization of Ca2+ signals induced in hippocampal CA1 neurones by the synaptic activation of NMDA receptors. J. Physiol. 469, 693–716.

    CAS  PubMed  Google Scholar 

  75. Emptage, N. (1999) Calcium on the up: supralinear calcium signaling in central neurons. Neuron 24, 727–737.

    Article  Google Scholar 

  76. Humbert, J. P., Matter, N., Artault, J. C., Koppler, P., and Malviya, A. N. (1996) Inositol 1,4,5-trisphosphate receptor is located to the inner nuclear membrane vindicating regulation of nuclear calcium signaling by inositol 1,4,5-trisphosphate-Discrete distribution of inositol phosphate receptors to inner and outer nuclear membranes. J. Biol. Chem. 271, 478–485.

    Article  CAS  PubMed  Google Scholar 

  77. Lipp, P., Thomas, D., Berridge, M. J., and Bootman, M. D. (1997) Nuclear calcium signalling by individual cytoplas-mic calcium puffs. EMBO J. 16, 7166–7173.

    Article  CAS  PubMed  Google Scholar 

  78. Nakazawa, H. and Murphy, T. H. (1999) Activation of nuclear calcium dynamics by synaptic stimulation in cultured cortical neurons. J. Neurochem. 73, 1075–1083.

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Preclinical Veterinary Studies, Edinburgh University, Edinburgh, UK

    Giles E. Hardingham

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  1. Clinical Physiological Medicine, and Medicine, Columbia University, New York, NY, USA

    Jahar Bhattacharya MBBS, DPhil (Professor of Physiology and Cellular Biophysics) (Professor of Physiology and Cellular Biophysics)

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© 2005 Humana Press Inc., Totowa, NJ

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Hardingham, G.E. (2005). Plasma Membrane-to-Nucleus Calcium Signaling. In: Bhattacharya, J. (eds) Cell Signaling in Vascular Inflammation. Humana Press. https://doi.org/10.1007/978-1-59259-909-7_16

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  • DOI: https://doi.org/10.1007/978-1-59259-909-7_16

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