Skip to main content
SpringerLink
Log in

Molecular Insights into Calcium Dependent Regulation of Ryanodine Receptor Calcium Release Channels

  • Chapter
  • First Online:
Calcium Signaling

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

Abstract

Ryanodine receptor calcium release channels (RyRs) play central roles in controlling intracellular calcium concentrations in excitable and non-excitable cells. RyRs are located in the sarcoplasmic or endoplasmic reticulum, intracellular Ca2+ storage compartment, and release Ca2+ during cellular action potentials or in response to other cellular stimuli. Mammalian cells express three structurally related isoforms of RyR. RyR1 and RyR2 are the major RyR isoforms in skeletal and cardiac muscle, respectively, and RyR3 is expressed in various tissues along with the other two isoforms. A prominent feature of RyRs is that the Ca2+ release channel activities of RyRs are regulated by calcium ions; therefore, intracellular Ca2+ release controls positive- and negative-feedback phenomena through the RyRs. RyR channel activities are also regulated by Ca2+ indirectly, i.e. through Ca2+ binding proteins at both cytosolic and sarco/endoplasmic reticulum luminal sides. Here, I summarize Ca2+-dependent feedback regulation of RyRs including recent progress in the structure/function aspects.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

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

    Article  CAS  PubMed  Google Scholar 

  2. Bootman MD (2012) Calcium signaling. Cold Spring Harb Perspect Biol 4(7):a011171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Berridge MJ (2016) The inositol trisphosphate/calcium signaling pathway in health and disease. Physiol Rev 96(4):1261–1296

    Article  CAS  PubMed  Google Scholar 

  4. Franzini-Armstrong C, Protasi F (1997) Ryanodine receptors of striated muscles: a complex channel capable of multiple interactions. Physiol Rev 77(3):699–729

    Article  CAS  PubMed  Google Scholar 

  5. Lanner JT, Georgiou DK, Joshi AD, Hamilton SL (2010) Ryanodine receptors: structure, expression, molecular details, and function in calcium release. Cold Spring Harb Perspect Biol 2(11):a003996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Meissner G (2017) The structural basis of ryanodine receptor ion channel function. J Gen Physiol 149(12):1065–1089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Inui M, Saito A, Fleischer S (1987) Purification of the ryanodine receptor and identity with feet structures of junctional terminal cisternae of sarcoplasmic reticulum from fast skeletal muscle. J Biol Chem 262(4):1740–1747

    CAS  PubMed  Google Scholar 

  8. Imagawa T, Smith JS, Coronado R, Campbell KP (1987) Purified ryanodine receptor from skeletal muscle sarcoplasmic reticulum is the Ca2+−permeable pore of the calcium release channel. J Biol Chem 262(34):16636–16643

    CAS  PubMed  Google Scholar 

  9. Lai FA, Erickson HP, Rousseau E, Liu QY, Meissner G (1988) Purification and reconstitution of the calcium release channel from skeletal muscle. Nature 331(6154):315–319

    Article  CAS  PubMed  Google Scholar 

  10. Anderson K, Lai FA, Liu QY, Rousseau E, Erickson HP, Meissner G (1989) Structural and functional characterization of the purified cardiac ryanodine receptor-Ca2+ release channel complex. J Biol Chem 264(2):1329–1335

    CAS  PubMed  Google Scholar 

  11. Takeshima H, Nishimura S, Matsumoto T, Ishida H, Kangawa K, Minamino N et al (1989) Primary structure and expression from complementary DNA of skeletal muscle ryanodine receptor. Nature 339(6224):439–445

    Article  CAS  PubMed  Google Scholar 

  12. Zorzato F, Fujii J, Otsu K, Phillips M, Green NM, Lai FA et al (1990) Molecular cloning of cDNA encoding human and rabbit forms of the Ca2+ release channel (ryanodine receptor) of skeletal muscle sarcoplasmic reticulum. J Biol Chem 265(4):2244–2256

    CAS  PubMed  Google Scholar 

  13. Otsu K, Willard HF, Khanna VK, Zorzato F, Green NM, MacLennan DH (1990) Molecular cloning of cDNA encoding the Ca2+ release channel (ryanodine receptor) of rabbit cardiac muscle sarcoplasmic reticulum. J Biol Chem 265(23):13472–13483

    CAS  PubMed  Google Scholar 

  14. Nakai J, Imagawa T, Hakamata Y, Shigekawa M, Takeshima H, Numa S (1990) Primary structure and functional expression from cDNA of the cardiac ryanodine receptor/calcium release channel. FEBS Lett 271(1–2):169–177

    Article  CAS  PubMed  Google Scholar 

  15. Hakamata Y, Nakai J, Takeshima H, Imoto K (1992) Primary structure and distribution of a novel ryanodine receptor/calcium release channel from rabbit brain. FEBS Lett 312(2–3):229–235

    Article  CAS  PubMed  Google Scholar 

  16. Takeshima H (1993) Primary structure and expression from cDNAs of the ryanodine receptor. Ann N Y Acad Sci 707:165–177

    Article  CAS  PubMed  Google Scholar 

  17. Furuichi T, Furutama D, Hakamata Y, Nakai J, Takeshima H, Mikoshiba K (1994) Multiple types of ryanodine receptor/Ca2+ release channels are differentially expressed in rabbit brain. J Neurosci 14(8):4794–4805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Conti A, Gorza L, Sorrentino V (1996) Differential distribution of ryanodine receptor type 3 (RyR3) gene product in mammalian skeletal muscles. Biochem J 316(Pt 1):19–23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Murayama T, Ogawa Y (1997) Characterization of type 3 ryanodine receptor (RyR3) of sarcoplasmic reticulum from rabbit skeletal muscles. J Biol Chem 272(38):24030–24037

    Article  CAS  PubMed  Google Scholar 

  20. Oyamada H, Murayama T, Takagi T, Iino M, Iwabe N, Miyata T et al (1994) Primary structure and distribution of ryanodine-binding protein isoforms of the bullfrog skeletal muscle. J Biol Chem 269(25):17206–17214

    CAS  PubMed  Google Scholar 

  21. Percival AL, Williams AJ, Kenyon JL, Grinsell MM, Airey JA, Sutko JL (1994) Chicken skeletal muscle ryanodine receptor isoforms: ion channel properties. Biophys J 67(5):1834–1850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ottini L, Marziali G, Conti A, Charlesworth A, Sorrentino V (1996) Alpha and beta isoforms of ryanodine receptor from chicken skeletal muscle are the homologues of mammalian RyR1 and RyR3. Biochem J 315(Pt 1):207–216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Du GG, Sandhu B, Khanna VK, Guo XH, MacLennan DH (2002) Topology of the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum (RyR1). Proc Natl Acad Sci U S A 99(26):16725–16730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Efremov RG, Leitner A, Aebersold R, Raunser S (2015) Architecture and conformational switch mechanism of the ryanodine receptor. Nature 517(7532):39–43

    Article  CAS  PubMed  Google Scholar 

  25. Zalk R, Clarke OB, des Georges A, Grassucci RA, Reiken S, Mancia F et al (2015) Structure of a mammalian ryanodine receptor. Nature 517(7532):44–49

    Article  CAS  PubMed  Google Scholar 

  26. Yan Z, Bai X, Yan C, Wu J, Li Z, Xie T et al (2015) Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution. Nature 517(7532):50–55

    Article  CAS  PubMed  Google Scholar 

  27. Peng W, Shen H, Wu J, Guo W, Pan X, Wang R et al (2016) Structural basis for the gating mechanism of the type 2 ryanodine receptor RyR2. Science 354(6310):aah5324

    Google Scholar 

  28. Zhong X, Liu Y, Zhu L, Meng X, Wang R, Van Petegem F et al (2013) Conformational dynamics inside amino-terminal disease hotspot of ryanodine receptor. Structure 21(11):2051–2060

    Article  CAS  PubMed  Google Scholar 

  29. Yuchi Z, Yuen SM, Lau K, Underhill AQ, Cornea RL, Fessenden JD et al (2015) Crystal structures of ryanodine receptor SPRY1 and tandem-repeat domains reveal a critical FKBP12 binding determinant. Nat Commun 6:7947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. des Georges A, Clarke OB, Zalk R, Yuan Q, Condon KJ, Grassucci RA et al (2016) Structural basis for gating and activation of RyR1. Cell 167(1):145–157. e17

    Google Scholar 

  31. Schneider MF, Chandler WK (1973) Voltage dependent charge movement of skeletal muscle: a possible step in excitation-contraction coupling. Nature 242(5395):244–246

    Article  CAS  PubMed  Google Scholar 

  32. Nabauer M, Callewaert G, Cleemann L, Morad M (1989) Regulation of calcium release is gated by calcium current, not gating charge, in cardiac myocytes. Science 244(4906):800–803

    Article  CAS  PubMed  Google Scholar 

  33. Ford LE, Podolsky RJ (1970) Regenerative calcium release within muscle cells. Science 167(3914):58–59

    Article  CAS  PubMed  Google Scholar 

  34. Endo M, Tanaka M, Ogawa Y (1970) Calcium induced release of calcium from the sarcoplasmic reticulum of skinned skeletal muscle fibres. Nature 228(5266):34–36

    Article  CAS  PubMed  Google Scholar 

  35. Brum G, Rios E, Stefani E (1988) Effects of extracellular calcium on calcium movements of excitation-contraction coupling in frog skeletal muscle fibres. J Physiol 398:441–473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Nakai J, Dirksen RT, Nguyen HT, Pessah IN, Beam KG, Allen PD (1996) Enhanced dihydropyridine receptor channel activity in the presence of ryanodine receptor. Nature 380(6569):72–75

    Article  CAS  PubMed  Google Scholar 

  37. Endo M (2009) Calcium-induced calcium release in skeletal muscle. Physiol Rev 89(4):1153–1176

    Article  CAS  PubMed  Google Scholar 

  38. Rios E (2018) Calcium-induced release of calcium in muscle: 50 years of work and the emerging consensus. J Gen Physiol 150(4):521–537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Murayama T, Kurebayashi N, Ogawa H, Yamazawa T, Oyamada H, Suzuki J et al (2016) Genotype-phenotype correlations of malignant hyperthermia and central Core disease mutations in the central region of the RYR1 channel. Hum Mutat 37(11):1231–1241

    Article  CAS  PubMed  Google Scholar 

  40. Meissner G (1994) Ryanodine receptor/Ca2+ release channels and their regulation by endogenous effectors. Annu Rev Physiol 56:485–508

    Article  CAS  PubMed  Google Scholar 

  41. Coronado R, Morrissette J, Sukhareva M, Vaughan DM (1994) Structure and function of ryanodine receptors. Am J Physiol 266(6 Pt 1):C1485–C1504

    Article  CAS  Google Scholar 

  42. Chen SR, Zhang L, MacLennan DH (1992) Characterization of a Ca2+ binding and regulatory site in the Ca2+ release channel (ryanodine receptor) of rabbit skeletal muscle sarcoplasmic reticulum. J Biol Chem 267(32):23318–23326

    CAS  PubMed  Google Scholar 

  43. Chen SR, Zhang L, MacLennan DH (1993) Antibodies as probes for Ca2+ activation sites in the Ca2+ release channel (ryanodine receptor) of rabbit skeletal muscle sarcoplasmic reticulum. J Biol Chem 268(18):13414–13421

    CAS  PubMed  Google Scholar 

  44. Chen SR, MacLennan DH (1994) Identification of calmodulin-, Ca2+-, and ruthenium red-binding domains in the Ca2+ release channel (ryanodine receptor) of rabbit skeletal muscle sarcoplasmic reticulum. J Biol Chem 269(36):22698–22704

    CAS  PubMed  Google Scholar 

  45. Chen SR, Ebisawa K, Li X, Zhang L (1998) Molecular identification of the ryanodine receptor Ca2+ sensor. J Biol Chem 273(24):14675–14678

    Article  CAS  PubMed  Google Scholar 

  46. Li P, Chen SR (2001) Molecular basis of Ca2+ activation of the mouse cardiac Ca2+ release channel (ryanodine receptor). J Gen Physiol 118(1):33–44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Fessenden JD, Chen L, Wang Y, Paolini C, Franzini-Armstrong C, Allen PD et al (2001) Ryanodine receptor point mutant E4032A reveals an allosteric interaction with ryanodine. Proc Natl Acad Sci U S A 98(5):2865–2870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Murayama T, Ogawa H, Kurebayashi N, Ohno S, Horie M, Sakurai T (2018) A tryptophan residue in the caffeine-binding site of the ryanodine receptor regulates Ca2+ sensitivity. Commun Biol 1:98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Xiong H, Feng X, Gao L, Xu L, Pasek DA, Seok JH et al (1998) Identification of a two EF-hand Ca2+ binding domain in lobster skeletal muscle ryanodine receptor/Ca2+ release channel. Biochemistry 37(14):4804–4814

    Article  CAS  PubMed  Google Scholar 

  50. Xiong L, Zhang JZ, He R, Hamilton SL (2006) A Ca2+-binding domain in RyR1 that interacts with the calmodulin binding site and modulates channel activity. Biophys J 90(1):173–182

    Article  CAS  PubMed  Google Scholar 

  51. Fessenden JD, Feng W, Pessah IN, Allen PD (2004) Mutational analysis of putative calcium binding motifs within the skeletal ryanodine receptor isoform, RyR1. J Biol Chem 279(51):53028–53035

    Article  CAS  PubMed  Google Scholar 

  52. Guo W, Sun B, Xiao Z, Liu Y, Wang Y, Zhang L et al (2016) The EF-hand Ca2+ binding domain is not required for cytosolic Ca2+ activation of the cardiac ryanodine receptor. J Biol Chem 291(5):2150–2160

    Article  CAS  PubMed  Google Scholar 

  53. Gomez AC, Yamaguchi N (2014) Two regions of the ryanodine receptor calcium channel are involved in Ca2+-dependent inactivation. Biochemistry 53(8):1373–1379

    Article  CAS  PubMed  Google Scholar 

  54. Xu L, Gomez AC, Pasek DA, Meissner G, Yamaguchi N (2017) Two EF-hand motifs in ryanodine receptor calcium release channels contribute to isoform-specific regulation by calmodulin. Cell Calcium 66:62–70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Chugun A, Sato O, Takeshima H, Ogawa Y (2007) Mg2+ activates the ryanodine receptor type 2 (RyR2) at intermediate Ca2+ concentrations. Am J Physiol Cell Physiol 292(1):C535–C544

    Article  CAS  PubMed  Google Scholar 

  56. Yamaguchi N, Xu L, Pasek DA, Evans KE, Meissner G (2003) Molecular basis of calmodulin binding to cardiac muscle Ca2+ release channel (ryanodine receptor). J Biol Chem 278(26):23480–23486

    Article  CAS  PubMed  Google Scholar 

  57. Laver DR, Baynes TM, Dulhunty AF (1997) Magnesium inhibition of ryanodine-receptor calcium channels: evidence for two independent mechanisms. J Membr Biol 156(3):213–229

    Article  CAS  PubMed  Google Scholar 

  58. Gomez AC, Holford TW, Yamaguchi N (2016) Malignant hyperthermia-associated mutations in the S2-S3 cytoplasmic loop of type 1 ryanodine receptor calcium channel impair calcium-dependent inactivation. Am J Physiol Cell Physiol 311(5):C749–C757

    Article  PubMed  PubMed Central  Google Scholar 

  59. Murayama T, Kurebayashi N, Ogawa Y (2000) Role of Mg2+ in Ca2+-induced Ca2+ release through ryanodine receptors of frog skeletal muscle: modulations by adenine nucleotides and caffeine. Biophys J 78(4):1810–1824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Tripathy A, Meissner G (1996) Sarcoplasmic reticulum lumenal Ca2+ has access to cytosolic activation and inactivation sites of skeletal muscle Ca2+ release channel. Biophys J 70(6):2600–2615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Xu L, Meissner G (1998) Regulation of cardiac muscle Ca2+ release channel by sarcoplasmic reticulum lumenal Ca2+. Biophys J 75(5):2302–2312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Du GG, MacLennan DH (1999) Ca2+ inactivation sites are located in the COOH-terminal quarter of recombinant rabbit skeletal muscle Ca2+ release channels (ryanodine receptors). J Biol Chem 274(37):26120–26126

    Article  CAS  PubMed  Google Scholar 

  63. Hayek SM, Zhu X, Bhat MB, Zhao J, Takeshima H, Valdivia HH et al (2000) Characterization of a calcium-regulation domain of the skeletal-muscle ryanodine receptor. Biochem J 351(Pt 1):57–65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Nakai J, Gao L, Xu L, Xin C, Pasek DA, Meissner G (1999) Evidence for a role of C-terminus in Ca2+ inactivation of skeletal muscle Ca2+ release channel (ryanodine receptor). FEBS Lett 459(2):154–158

    Article  CAS  PubMed  Google Scholar 

  65. Du GG, Khanna VK, MacLennan DH (2000) Mutation of divergent region 1 alters caffeine and Ca2+ sensitivity of the skeletal muscle Ca2+ release channel (ryanodine receptor). J Biol Chem 275(16):11778–11783

    Article  CAS  PubMed  Google Scholar 

  66. Fabiato A, Fabiato F (1979) Calcium and cardiac excitation-contraction coupling. Annu Rev Physiol 41:473–484

    Article  CAS  PubMed  Google Scholar 

  67. Orchard CH, Eisner DA, Allen DG (1983) Oscillations of intracellular Ca2+ in mammalian cardiac muscle. Nature 304(5928):735–738

    Article  CAS  PubMed  Google Scholar 

  68. Jiang D, Xiao B, Yang D, Wang R, Choi P, Zhang L et al (2004) RyR2 mutations linked to ventricular tachycardia and sudden death reduce the threshold for store-overload-induced Ca2+ release (SOICR). Proc Natl Acad Sci U S A 101(35):13062–13067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Jiang D, Wang R, Xiao B, Kong H, Hunt DJ, Choi P et al (2005) Enhanced store overload-induced Ca2+ release and channel sensitivity to luminal Ca2+ activation are common defects of RyR2 mutations linked to ventricular tachycardia and sudden death. Circ Res 97(11):1173–1181

    Article  CAS  PubMed  Google Scholar 

  70. Jiang D, Chen W, Xiao J, Wang R, Kong H, Jones PP et al (2008) Reduced threshold for luminal Ca2+ activation of RyR1 underlies a causal mechanism of porcine malignant hyperthermia. J Biol Chem 283(30):20813–20820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Chen W, Wang R, Chen B, Zhong X, Kong H, Bai Y et al (2014) The ryanodine receptor store-sensing gate controls Ca2+ waves and Ca2+-triggered arrhythmias. Nat Med 20(2):184–192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Saimi Y, Kung C (2002) Calmodulin as an ion channel subunit. Annu Rev Physiol 64:289–311

    Article  CAS  PubMed  Google Scholar 

  73. Tripathy A, Xu L, Mann G, Meissner G (1995) Calmodulin activation and inhibition of skeletal muscle Ca2+ release channel (ryanodine receptor). Biophys J 69(1):106–119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Buratti R, Prestipino G, Menegazzi P, Treves S, Zorzato F (1995) Calcium dependent activation of skeletal muscle Ca2+ release channel (ryanodine receptor) by calmodulin. Biochem Biophys Res Commun 213(3):1082–1090

    Article  CAS  PubMed  Google Scholar 

  75. Chen SR, Li X, Ebisawa K, Zhang L (1997) Functional characterization of the recombinant type 3 Ca2+ release channel (ryanodine receptor) expressed in HEK293 cells. J Biol Chem 272(39):24234–24246

    Article  CAS  PubMed  Google Scholar 

  76. Fruen BR, Bardy JM, Byrem TM, Strasburg GM, Louis CF (2000) Differential Ca2+ sensitivity of skeletal and cardiac muscle ryanodine receptors in the presence of calmodulin. Am J Physiol Cell Physiol 279(3):C724–C733

    Article  CAS  PubMed  Google Scholar 

  77. Balshaw DM, Xu L, Yamaguchi N, Pasek DA, Meissner G (2001) Calmodulin binding and inhibition of cardiac muscle calcium release channel (ryanodine receptor). J Biol Chem 276(23):20144–20153

    Article  CAS  PubMed  Google Scholar 

  78. Yamaguchi N, Xu L, Pasek DA, Evans KE, Chen SR, Meissner G (2005) Calmodulin regulation and identification of calmodulin binding region of type-3 ryanodine receptor calcium release channel. Biochemistry 44(45):15074–15081

    Article  CAS  PubMed  Google Scholar 

  79. Ono M, Yano M, Hino A, Suetomi T, Xu X, Susa T et al (2010) Dissociation of calmodulin from cardiac ryanodine receptor causes aberrant Ca2+ release in heart failure. Cardiovasc Res 87(4):609–617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Terentyev D, Gyorke I, Belevych AE, Terentyeva R, Sridhar A, Nishijima Y et al (2008) Redox modification of ryanodine receptors contributes to sarcoplasmic reticulum Ca2+ leak in chronic heart failure. Circ Res 103(12):1466–1472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Oda T, Yang Y, Uchinoumi H, Thomas DD, Chen-Izu Y, Kato T et al (2015) Oxidation of ryanodine receptor (RyR) and calmodulin enhance Ca release and pathologically alter, RyR structure and calmodulin affinity. J Mol Cell Cardiol 85:240–248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Yamaguchi N, Xin C, Meissner G (2001) Identification of apocalmodulin and Ca2+-calmodulin regulatory domain in skeletal muscle Ca2+ release channel, ryanodine receptor. J Biol Chem 276(25):22579–22585

    Article  CAS  PubMed  Google Scholar 

  83. Moore CP, Rodney G, Zhang JZ, Santacruz-Toloza L, Strasburg G, Hamilton SL (1999) Apocalmodulin and Ca2+ calmodulin bind to the same region on the skeletal muscle Ca2+ release channel. Biochemistry 38(26):8532–8537

    Article  CAS  PubMed  Google Scholar 

  84. Rodney GG, Moore CP, Williams BY, Zhang JZ, Krol J, Pedersen SE et al (2001) Calcium binding to calmodulin leads to an N-terminal shift in its binding site on the ryanodine receptor. J Biol Chem 276(3):2069–2074

    Article  CAS  PubMed  Google Scholar 

  85. Maximciuc AA, Putkey JA, Shamoo Y, Mackenzie KR (2006) Complex of calmodulin with a ryanodine receptor target reveals a novel, flexible binding mode. Structure 14(10):1547–1556

    Article  CAS  PubMed  Google Scholar 

  86. Menegazzi P, Larini F, Treves S, Guerrini R, Quadroni M, Zorzato F (1994) Identification and characterization of three calmodulin binding sites of the skeletal muscle ryanodine receptor. Biochemistry 33(31):9078–9084

    Article  CAS  PubMed  Google Scholar 

  87. Guerrini R, Menegazzi P, Anacardio R, Marastoni M, Tomatis R, Zorzato F et al (1995) Calmodulin binding sites of the skeletal, cardiac, and brain ryanodine receptor Ca2+ channels: modulation by the catalytic subunit of cAMP-dependent protein kinase? Biochemistry 34(15):5120–5129

    Article  CAS  PubMed  Google Scholar 

  88. Lau K, Chan MM, Van Petegem F (2014) Lobe-specific calmodulin binding to different ryanodine receptor isoforms. Biochemistry 53(5):932–946

    Article  CAS  PubMed  Google Scholar 

  89. Yamaguchi N, Takahashi N, Xu L, Smithies O, Meissner G (2007) Early cardiac hypertrophy in mice with impaired calmodulin regulation of cardiac muscle Ca2+ release channel. J Clin Invest 117(5):1344–1353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Yamaguchi N, Xu L, Evans KE, Pasek DA, Meissner G (2004) Different regions in skeletal and cardiac muscle ryanodine receptors are involved in transducing the functional effects of calmodulin. J Biol Chem 279(35):36433–36439

    Article  CAS  PubMed  Google Scholar 

  91. Samso M, Wagenknecht T (2002) Apocalmodulin and Ca2+-calmodulin bind to neighboring locations on the ryanodine receptor. J Biol Chem 277(2):1349–1353

    Article  CAS  PubMed  Google Scholar 

  92. Arnaiz-Cot JJ, Damon BJ, Zhang XH, Cleemann L, Yamaguchi N, Meissner G et al (2013) Cardiac calcium signalling pathologies associated with defective calmodulin regulation of type 2 ryanodine receptor. J Physiol 591(17):4287–4299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Yamaguchi N, Chakraborty A, Huang TQ, Xu L, Gomez AC, Pasek DA et al (2013) Cardiac hypertrophy associated with impaired regulation of cardiac ryanodine receptor by calmodulin and S100A1. Am J Physiol Heart Circ Physiol 305(1):H86–H94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Yamaguchi N, Prosser BL, Ghassemi F, Xu L, Pasek DA, Eu JP et al (2011) Modulation of sarcoplasmic reticulum Ca2+ release in skeletal muscle expressing ryanodine receptor impaired in regulation by calmodulin and S100A1. Am J Physiol Cell Physiol 300(5):C998–C1012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Nyegaard M, Overgaard MT, Sondergaard MT, Vranas M, Behr ER, Hildebrandt LL et al (2012) Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death. Am J Hum Genet 91(4):703–712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Hwang HS, Nitu FR, Yang Y, Walweel K, Pereira L, Johnson CN et al (2014) Divergent regulation of ryanodine receptor 2 calcium release channels by arrhythmogenic human calmodulin missense mutants. Circ Res 114(7):1114–1124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Sondergaard MT, Tian X, Liu Y, Wang R, Chazin WJ, Chen SR et al (2015) Arrhythmogenic calmodulin mutations affect the activation and termination of cardiac ryanodine receptor-mediated Ca2+ release. J Biol Chem 290(43):26151–26162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Vassilakopoulou V, Calver BL, Thanassoulas A, Beck K, Hu H, Buntwal L et al (2015) Distinctive malfunctions of calmodulin mutations associated with heart RyR2-mediated arrhythmic disease. Biochim Biophys Acta 1850(11):2168–2176

    Article  CAS  PubMed  Google Scholar 

  99. Liu B, Walton SD, Ho HT, Belevych AE, Tikunova SB, Bonilla I et al (2018) Gene transfer of engineered calmodulin alleviates ventricular arrhythmias in a calsequestrin-associated mouse model of catecholaminergic polymorphic ventricular tachycardia. J Am Heart Assoc 7(10):e008155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Treves S, Scutari E, Robert M, Groh S, Ottolia M, Prestipino G et al (1997) Interaction of S100A1 with the Ca2+ release channel (ryanodine receptor) of skeletal muscle. Biochemistry 36(38):11496–11503

    Article  CAS  PubMed  Google Scholar 

  101. Most P, Remppis A, Pleger ST, Loffler E, Ehlermann P, Bernotat J et al (2003) Transgenic overexpression of the Ca2+-binding protein S100A1 in the heart leads to increased in vivo myocardial contractile performance. J Biol Chem 278(36):33809–33817

    Article  CAS  PubMed  Google Scholar 

  102. Volkers M, Rohde D, Goodman C, Most P (2010) S100A1: a regulator of striated muscle sarcoplasmic reticulum Ca2+ handling, sarcomeric, and mitochondrial function. J Biomed Biotechnol 2010:178614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Prosser BL, Hernandez-Ochoa EO, Schneider MF (2011) S100A1 and calmodulin regulation of ryanodine receptor in striated muscle. Cell Calcium 50(4):323–331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Prosser BL, Wright NT, Hernandez-Ochoa EO, Varney KM, Liu Y, Olojo RO et al (2008) S100A1 binds to the calmodulin-binding site of ryanodine receptor and modulates skeletal muscle excitation-contraction coupling. J Biol Chem 283(8):5046–5057

    Article  CAS  PubMed  Google Scholar 

  105. Wright NT, Prosser BL, Varney KM, Zimmer DB, Schneider MF, Weber DJ (2008) S100A1 and calmodulin compete for the same binding site on ryanodine receptor. J Biol Chem 283(39):26676–26683

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Rebbeck RT, Nitu FR, Rohde D, Most P, Bers DM, Thomas DD et al (2016) S100A1 protein does not compete with calmodulin for ryanodine receptor binding but structurally alters the ryanodine receptor.Calmodulin complex. J Biol Chem 291(30):15896–15907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Saito A, Seiler S, Chu A, Fleischer S (1984) Preparation and morphology of sarcoplasmic reticulum terminal cisternae from rabbit skeletal muscle. J Cell Biol 99(3):875–885

    Article  CAS  PubMed  Google Scholar 

  108. Franzini-Armstrong C, Kenney LJ, Varriano-Marston E (1987) The structure of calsequestrin in triads of vertebrate skeletal muscle: a deep-etch study. J Cell Biol 105(1):49–56

    Article  CAS  PubMed  Google Scholar 

  109. Guo W, Campbell KP (1995) Association of triadin with the ryanodine receptor and calsequestrin in the lumen of the sarcoplasmic reticulum. J Biol Chem 270(16):9027–9030

    Article  CAS  PubMed  Google Scholar 

  110. Zhang L, Kelley J, Schmeisser G, Kobayashi YM, Jones LR (1997) Complex formation between junctin, triadin, calsequestrin, and the ryanodine receptor. Proteins of the cardiac junctional sarcoplasmic reticulum membrane. J Biol Chem 272(37):23389–23397

    Article  CAS  PubMed  Google Scholar 

  111. Kobayashi YM, Alseikhan BA, Jones LR (2000) Localization and characterization of the calsequestrin-binding domain of triadin 1. Evidence for a charged beta-strand in mediating the protein-protein interaction. J Biol Chem 275(23):17639–17646

    Article  CAS  PubMed  Google Scholar 

  112. Handhle A, Ormonde CE, Thomas NL, Bralesford C, Williams AJ, Lai FA et al (2016) Calsequestrin interacts directly with the cardiac ryanodine receptor luminal domain. J Cell Sci 129(21):3983–3988

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Beard NA, Sakowska MM, Dulhunty AF, Laver DR (2002) Calsequestrin is an inhibitor of skeletal muscle ryanodine receptor calcium release channels. Biophys J 82(1 Pt 1):310–320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Gyorke I, Hester N, Jones LR, Gyorke S (2004) The role of calsequestrin, triadin, and junctin in conferring cardiac ryanodine receptor responsiveness to luminal calcium. Biophys J 86(4):2121–2128

    Article  PubMed  PubMed Central  Google Scholar 

  115. Beard NA, Casarotto MG, Wei L, Varsanyi M, Laver DR, Dulhunty AF (2005) Regulation of ryanodine receptors by calsequestrin: effect of high luminal Ca2+ and phosphorylation. Biophys J 88(5):3444–3454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Paolini C, Quarta M, Nori A, Boncompagni S, Canato M, Volpe P et al (2007) Reorganized stores and impaired calcium handling in skeletal muscle of mice lacking calsequestrin-1. J Physiol 583(Pt 2):767–784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Lahat H, Pras E, Olender T, Avidan N, Ben-Asher E, Man O et al (2001) A missense mutation in a highly conserved region of CASQ2 is associated with autosomal recessive catecholamine-induced polymorphic ventricular tachycardia in bedouin families from Israel. Am J Hum Genet 69(6):1378–1384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Postma AV, Denjoy I, Hoorntje TM, Lupoglazoff JM, Da Costa A, Sebillon P et al (2002) Absence of calsequestrin 2 causes severe forms of catecholaminergic polymorphic ventricular tachycardia. Circ Res 91(8):e21–e26

    Article  CAS  PubMed  Google Scholar 

  119. Knollmann BC, Chopra N, Hlaing T, Akin B, Yang T, Ettensohn K et al (2006) Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca2+ release, and catecholaminergic polymorphic ventricular tachycardia. J Clin Invest 116(9):2510–2520

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Song L, Alcalai R, Arad M, Wolf CM, Toka O, Conner DA et al (2007) Calsequestrin 2 (CASQ2) mutations increase expression of calreticulin and ryanodine receptors, causing catecholaminergic polymorphic ventricular tachycardia. J Clin Invest 117(7):1814–1823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC et al (2004) UCSF chimera–a visualization system for exploratory research and analysis. J Comput Chem 25(13):1605–1612

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

I would like to appreciate Dr. Gerhard Meissner for his mentorship on RyR structure/function analysis when I was working in his laboratory and for his continuous advices and encouragements on my current studies. I am very thankful to Dr. Martin Morad, the director of Cardiac Signaling Center, for providing me with wonderful environment to study Ca2+ signaling, and valuable suggestions and discussions on my studies. I am also grateful to Angela C. Gomez and Jordan S. Carter for their contributions to the RyR mutagenesis studies in my laboratory and for the comments on this manuscript. This study was supported by National Institutes of Health Grants R03AR061030, P20GM103499, and UL1TR001450.

Author information

Authors and Affiliations

  1. Cardiac Signaling Center, University of South Carolina, Medical University of South Carolina and Clemson University, Charleston, SC, USA

    Naohiro Yamaguchi

  2. Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA

    Naohiro Yamaguchi

Authors
  1. Naohiro Yamaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Naohiro Yamaguchi .

Editor information

Editors and Affiliations

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

    Md. Shahidul Islam

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Yamaguchi, N. (2020). Molecular Insights into Calcium Dependent Regulation of Ryanodine Receptor Calcium Release Channels. 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_13

Download citation

Publish with us

Policies and ethics

Search

Navigation