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Calcium Signaling and Gene Expression

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Calcium Signaling

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1131))

Abstract

Calcium signaling plays an important role in gene expression. At the transcriptional level, this may underpin mammalian neuronal synaptic plasticity. Calcium influx into the postsynaptic neuron via: N-methyl-D-aspartate (NMDA) receptors activates small GTPase Rac1 and other Rac guanine nucleotide exchange factors, and stimulates calmodulin-dependent kinase kinase (CaMKK) and CaMKI; α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors that are not impermeable to calcium ions, that is, those lacking the glutamate receptor-2 subunits, leads to activation of Ras guanine nucleotide-releasing factor proteins, which is coupled with activation of the mitogen-activated protein kinases/extracellular signal-regulated kinases signaling cascade; L-type voltage-gated calcium channels activates signaling pathways involving CaMKII, downstream responsive element antagonist modulator and distinct microdomains. Key members of these signaling cascades then translocate into the nucleus, where they alter the expression of genes involved in neuronal synaptic plasticity. At the post-transcriptional level, intracellular calcium level changes can change alternative splicing patterns; in the mammalian brain, alterations in calcium signaling via NMDA receptors is associated with exon silencing of the CI cassette of the NMDA R1 receptor (GRIN1) transcript by UAGG motifs in response to neuronal excitation. Regulation also occurs at the translational level; transglutaminase-2 (TG2) mediates calcium ion-regulated crosslinking of Y-box binding protein-1 (YB-1) translation-regulatory protein in TGFβ1-activated myofibroblasts; YB-1 binds smooth muscle α-actin mRNA and regulates its translational activity. Calcium signaling is also important in epigenetic regulation, for example in respect of changes in cytosine bases. Targeting calcium signaling may provide therapeutically useful options, for example to induce epigenetic reactivation of tumor suppressor genes in cancer patients.

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References

  1. Krebs JE, Goldstein ES, Kilpatrick ST (2018) Lewin’s genes XII. Jones & Bartlett Learning, Burlington

    Google Scholar 

  2. Clapham DE (2007) Calcium signaling. Cell 131(6):1047–1058

    CAS  PubMed  Google Scholar 

  3. Westheimer FH (1987) Why nature chose phosphates. Science 235(4793):1173–1178

    Article  CAS  PubMed  Google Scholar 

  4. Morris G, Puri BK, Walder K, Berk M, Stubbs B, Maes M et al (2018) The endoplasmic reticulum stress response in neuroprogressive diseases: emerging pathophysiological role and translational implications. Mol Neurobiol 55(12):8765–8787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Puri BK, Morris G (2018) Potential therapeutic interventions based on the role of the endoplasmic reticulum stress response in progressive neurodegenerative diseases. Neural Regen Res 13(11):1887–1889

    Article  PubMed  PubMed Central  Google Scholar 

  6. Berridge MJ, Lipp P, Bootman MD (2000) The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 1:11

    Article  CAS  PubMed  Google Scholar 

  7. Putney JW, Tomita T (2012) Phospholipase C signaling and calcium influx. Adv Biol Regul 52(1):152–164

    Article  CAS  PubMed  Google Scholar 

  8. Greer PL, Greenberg ME (2008) From synapse to nucleus: calcium-dependent gene transcription in the control of synapse development and function. Neuron 59(6):846–860

    Article  CAS  PubMed  Google Scholar 

  9. Berridge MJ (1998) Neuronal calcium signaling. Neuron 21(1):13–26

    Article  CAS  PubMed  Google Scholar 

  10. Berridge MJ, Bootman MD, Lipp P (1998) Calcium–a life and death signal. Nature 395(6703):645–648

    Article  CAS  PubMed  Google Scholar 

  11. Jonas P, Burnashev N (1995) Molecular mechanisms controlling calcium entry through AMPA-type glutamate receptor channels. Neuron 15(5):987–990

    Article  CAS  PubMed  Google Scholar 

  12. Xie Z, Srivastava DP, Photowala H, Kai L, Cahill ME, Woolfrey KM et al (2007) Kalirin-7 controls activity-dependent structural and functional plasticity of dendritic spines. Neuron 56(4):640–656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Saneyoshi T, Wayman G, Fortin D, Davare M, Hoshi N, Nozaki N et al (2008) Activity-dependent synaptogenesis: regulation by a CaM-kinase kinase/CaM-kinase I/betaPIX signaling complex. Neuron 57(1):94–107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tian X, Feig LA (2006) Age-dependent participation of Ras-GRF proteins in coupling calcium-permeable AMPA glutamate receptors to Ras/Erk signaling in cortical neurons. J Biol Chem 281(11):7578–7582

    Article  CAS  PubMed  Google Scholar 

  15. Naranjo JR, Mellström B (2012) Ca2+-dependent transcriptional control of Ca2+ homeostasis. J Biol Chem 287(38):31674–31680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Takasu MA, Dalva MB, Zigmond RE, Greenberg ME (2002) Modulation of NMDA receptor-dependent calcium influx and gene expression through EphB receptors. Science 295(5554):491–495

    Article  CAS  PubMed  Google Scholar 

  17. Cartwright EJ, Oceandy D, Austin C, Neyses L (2011) Ca2+ signalling in cardiovascular disease: the role of the plasma membrane calcium pumps. Sci China Life Sci 54(8):691–698

    Article  CAS  PubMed  Google Scholar 

  18. Jain M, Shrager J, Harris EH, Halbrook R, Grossman AR, Hauser C et al (2007) EST assembly supported by a draft genome sequence: an analysis of the Chlamydomonas reinhardtii transcriptome. Nucleic Acids Res 35(6):2074–2083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Merchant SS, Prochnik SE, Vallon O, Harris EH, Karpowicz SJ, Witman GB et al (2007) The Chlamydomonas genome reveals the evolution of key animal and plant functions. Science 318(5848):245–250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Misumi O, Yoshida Y, Nishida K, Fujiwara T, Sakajiri T, Hirooka S et al (2008) Genome analysis and its significance in four unicellular algae, Cyanidioschyzon [corrected] merolae, Ostreococcus tauri, Chlamydomonas reinhardtii, and Thalassiosira pseudonana. J Plant Res 121(1):3–17

    Article  CAS  PubMed  Google Scholar 

  21. Rea G, Antonacci A, Lambreva MD, Mattoo AK (2018) Features of cues and processes during chloroplast-mediated retrograde signaling in the alga Chlamydomonas. Plant Sci 272:193–206

    Article  CAS  PubMed  Google Scholar 

  22. An P, Grabowski PJ (2007) Exon silencing by UAGG motifs in response to neuronal excitation. PLoS Biol 5(2):e36

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Black DL, Grabowski PJ (2003) Alternative pre-mRNA splicing and neuronal function. Prog Mol Subcell Biol 31:187–216

    Article  CAS  PubMed  Google Scholar 

  24. Zukin RS, Bennett MV (1995) Alternatively spliced isoforms of the NMDARI receptor subunit. Trends Neurosci 18(7):306–313

    Article  CAS  PubMed  Google Scholar 

  25. Black DL (1998) Splicing in the inner ear: a familiar tune, but what are the instruments? Neuron 20(2):165–168

    Article  CAS  PubMed  Google Scholar 

  26. Navaratnam DS, Bell TJ, Tu TD, Cohen EL, Oberholtzer JC (1997) Differential distribution of Ca2+−activated K+ channel splice variants among hair cells along the tonotopic axis of the chick cochlea. Neuron 19(5):1077–1085

    Article  CAS  PubMed  Google Scholar 

  27. Rosenblatt KP, Sun ZP, Heller S, Hudspeth AJ (1997) Distribution of Ca2+−activated K+ channel isoforms along the tonotopic gradient of the chicken’s cochlea. Neuron 19(5):1061–1075

    Article  CAS  PubMed  Google Scholar 

  28. Xie J, Black DL (2001) A CaMK IV responsive RNA element mediates depolarization-induced alternative splicing of ion channels. Nature 410(6831):936–939

    Article  CAS  PubMed  Google Scholar 

  29. Tuluc P, Yarov-Yarovoy V, Benedetti B, Flucher BE (2016) Molecular interactions in the voltage sensor controlling gating properties of CaV calcium channels. Structure 24(2):261–271

    Article  CAS  PubMed  Google Scholar 

  30. Coste de Bagneaux P, Campiglio M, Benedetti B, Tuluc P, Flucher BE (2018) Role of putative voltage-sensor countercharge D4 in regulating gating properties of CaV1.2 and CaV1.3 calcium channels. Channels (Austin) 12(1):249–261

    Article  Google Scholar 

  31. Canney PA, Dean S (1990) Transforming growth factor beta: a promotor of late connective tissue injury following radiotherapy? Br J Radiol 63(752):620–623

    Article  CAS  PubMed  Google Scholar 

  32. Sun X, Liu W, Cheng G, Qu X, Bi H, Cao Z et al (2017) The influence of connective tissue growth factor on rabbit ligament injury repair. Bone Joint Res 6(7):399–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Toomey D, Condron C, Wu QD, Kay E, Harmey J, Broe P et al (2001) TGF-beta1 is elevated in breast cancer tissue and regulates nitric oxide production from a number of cellular sources during hypoxia re-oxygenation injury. Br J Biomed Sci 58(3):177–183

    CAS  PubMed  Google Scholar 

  34. Wang S, Denichilo M, Brubaker C, Hirschberg R (2001) Connective tissue growth factor in tubulointerstitial injury of diabetic nephropathy. Kidney Int 60(1):96–105

    Article  CAS  PubMed  Google Scholar 

  35. Desmouliere A, Geinoz A, Gabbiani F, Gabbiani G (1993) Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol 122(1):103–111

    Article  CAS  PubMed  Google Scholar 

  36. Gabbiani G (2003) The myofibroblast in wound healing and fibrocontractive diseases. J Pathol 200(4):500–503

    Article  CAS  PubMed  Google Scholar 

  37. Grotendorst GR, Rahmanie H, Duncan MR (2004) Combinatorial signaling pathways determine fibroblast proliferation and myofibroblast differentiation. FASEB J 18(3):469–479

    Article  CAS  PubMed  Google Scholar 

  38. Chen G, Grotendorst G, Eichholtz T, Khalil N (2003) GM-CSF increases airway smooth muscle cell connective tissue expression by inducing TGF-beta receptors. Am J Phys Lung Cell Mol Phys 284(3):L548–L556

    CAS  Google Scholar 

  39. Willis WL, Hariharan S, David JJ, Strauch AR (2013) Transglutaminase-2 mediates calcium-regulated crosslinking of the Y-Box 1 (YB-1) translation-regulatory protein in TGFβ1-activated myofibroblasts. J Cell Biochem 114(12):2753–2769

    Article  CAS  PubMed  Google Scholar 

  40. Tollefsbol TO (2016) An overview of medical epigenetics. In: Tollefsbol TO (ed) Medical epigenetics. Elsevier, Amsterdam, pp 3–7

    Chapter  Google Scholar 

  41. Kanwal R, Gupta K, Gupta S (2015) Cancer epigenetics: an introduction. Methods Mol Biol 1238:3–25

    Article  PubMed  Google Scholar 

  42. Huang B, Jiang C, Zhang R (2014) Epigenetics: the language of the cell? Epigenomics 6(1):73–88

    Article  PubMed  CAS  Google Scholar 

  43. Takaya J, Iharada A, Okihana H, Kaneko K (2013) A calcium-deficient diet in pregnant, nursing rats induces hypomethylation of specific cytosines in the 11beta-hydroxysteroid dehydrogenase-1 promoter in pup liver. Nutr Res 33(11):961–970

    Article  CAS  PubMed  Google Scholar 

  44. Raynal NJ, Lee JT, Wang Y, Beaudry A, Madireddi P, Garriga J et al (2016) Targeting calcium signaling induces epigenetic reactivation of tumor suppressor genes in cancer. Cancer Res 76(6):1494–1505

    Article  CAS  PubMed  Google Scholar 

  45. Martinowich K, Hattori D, Wu H, Fouse S, He F, Hu Y et al (2003) DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science 302(5646):890–893

    Article  CAS  PubMed  Google Scholar 

  46. Chen WG, Chang Q, Lin Y, Meissner A, West AE, Griffith EC et al (2003) Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science 302(5646):885–889

    Article  CAS  PubMed  Google Scholar 

  47. Nagy C, Vaillancourt K, Turecki G (2018) A role for activity-dependent epigenetics in the development and treatment of major depressive disorder. Genes Brain Behav 17(3):e12446

    Article  CAS  PubMed  Google Scholar 

  48. Kao YH, Cheng CC, Chen YC, Chung CC, Lee TI, Chen SA et al (2011) Hydralazine-induced promoter demethylation enhances sarcoplasmic reticulum Ca2+ -ATPase and calcium homeostasis in cardiac myocytes. Lab Investig 91(9):1291–1297

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. CAR, Cambridge, UK

    Basant K. Puri

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  1. Basant K. Puri
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Correspondence to Basant K. Puri .

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Editors and Affiliations

  1. Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden

    Md. Shahidul Islam

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Puri, B.K. (2020). Calcium Signaling and Gene Expression. In: Islam, M. (eds) Calcium Signaling. Advances in Experimental Medicine and Biology, vol 1131. Springer, Cham. https://doi.org/10.1007/978-3-030-12457-1_22

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