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Insights into the Three-Dimensional Organization of Ryanodine Receptors

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Handbook of Neurochemistry and Molecular Neurobiology

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Abstract

The ryanodine receptor encompasses a high-conductance calcium channel that plays a critical role in intracellular calcium signalling and its dysfunction has been implicated in numerous cardiovascular and neuromuscular disorders. Here, we discuss the various pathologies associated with aberrant ryanodine receptor function and our current understanding of the intricate topological organisation of this the largest known ion channel complex.

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Abbreviations

APP:

amyloid precursor protein

ARVC:

arrhythmogenic right ventricular cardiomyopathy

CaMKII:

Ca2+/calmodulin-dependent kinase

CICR:

Ca2+-induced Ca2+ release

CaM:

calmodulin

CPVT:

catecholaminergic polymorphic ventricular tachycardia

CCD:

central core disease

CPK:

conventional protein kinase

cryo-EM:

cryo-electron microscopy

CRISP:

cysteine-rich secretory protein

Kd:

dissociation constant

DR1, DR2, and DR3:

divergent regions 1, 2, and 3

FAD:

familial Alzheimer’s disease

FKBP:

FK506 binding protein

IpTxa:

imperatoxin A

IP3R:

inositol trisphosphate receptor

ITC:

isothermal titration calorimetry

MH:

malignant hyperthermia

MIR:

mannosyltransferase, IP3R and RyR

PS1:

presenilin 1

PKA:

protein kinase A

RyR:

ryanodine receptor

RIH:

RyR and IP3-homology

SPRY:

splA and ryanodine receptor

SOCS:

suppressor of cytokine signaling

TM:

transmembrane

References

  • Ahern GP, Junankar PR, Dulhunty AF. 1994. Single channel activity of the ryanodine receptor calcium release channel is modulated by FK-506. FEBS Lett 352(3): 369–374.

    Article  PubMed  CAS  Google Scholar 

  • Bers DM. 2004. Macromolecular complexes regulating cardiac ryanodine receptor function. J Mol Cell Cardiol. 37(2): 417–429.

    Article  PubMed  CAS  Google Scholar 

  • Block BA, Imagawa T, Campbell KP, Franzini-Armstrong C. 1988. Structural evidence for direct interaction between the molecular components of the transverse tubule/sarcoplasmic reticulum junction in skeletal muscle. J Cell Biol 107(6 Pt 2): 2587–2600.

    Article  PubMed  CAS  Google Scholar 

  • Bosanac I, Alattia JR, Mal TK, Chan J, Talarico S, et al. 2002. Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand. Nature 420(6916): 696–700.

    Article  PubMed  CAS  Google Scholar 

  • Brandt NR, Caswell AH, Brandt T, Brew K, Mellgren RL. 1992. Mapping of the calpain proteolysis products of the junctional foot protein of the skeletal muscle triad junction. J Membr Biol 127(1): 35–47.

    PubMed  CAS  Google Scholar 

  • Brillantes AB, Ondrias K, Scott A, Kobrinsky E, Ondriasova E, et al. 1994. Stabilization of calcium release channel (ryanodine receptor) function by FK506-binding protein. Cell 77(4): 513–523.

    Article  PubMed  CAS  Google Scholar 

  • Bultynck G, De Smet P, Rossi D, Callewaert G, Missiaen L, et al. 2001a. Characterization and mapping of the 12 kDa FK506-binding protein (FKBP12)-binding site on different isoforms of the ryanodine receptor and of the inositol 1,4,5-trisphosphate receptor. Biochem J 354(Pt 2): 413–422.

    Article  PubMed  CAS  Google Scholar 

  • Bultynck G, Rossi D, Callewaert G, Missiaen L, Sorrentino V, et al. 2001b. The conserved sites for the FK506-binding proteins in ryanodine receptors and inositol 1,4,5-trisphosphate receptors are structurally and functionally different. J Biol Chem 276(50): 47715–47724.

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Cameron AM, Nucifora FC, Jr., Fung ET, Livingston DJ, Aldape RA, et al. 1997. FKBP12 binds the inositol 1,4,5-trisphosphate receptor at leucine-proline (1400–1401) and anchors calcineurin to this FK506-like domain. J Biol Chem 272(44): 27582–27588.

    Article  PubMed  CAS  Google Scholar 

  • Chen SR, Li P, Zhao M, Li X, Zhang L. 2002. Role of the proposed pore-forming segment of the Ca2+ release channel (ryanodine receptor) in ryanodine interaction. Biophys J 82(5): 2436–2447.

    Article  PubMed  CAS  Google Scholar 

  • Cozzone AJ. 1988. Protein phosphorylation in prokaryotes. Annu Rev Microbiol 42: 97–125.

    Article  PubMed  CAS  Google Scholar 

  • Davison FD, D’Cruz LG, McKenna WJ. 2000. Molecular motors in the heart. Essays Biochem 35: 145–158.

    PubMed  CAS  Google Scholar 

  • Du GG, Avila G, Sharma P, Khanna VK, Dirksen RT, et al. 2004. Role of the sequence surrounding predicted transmembrane helix M4 in membrane association and function of the Ca(2+) release channel of skeletal muscle sarcoplasmic reticulum (ryanodine receptor isoform 1). J Biol Chem 279(36): 37566–37574.

    Article  PubMed  CAS  Google Scholar 

  • Du GG, Guo X, Khanna VK, MacLennan DH. 2001. Functional characterization of mutants in the predicted pore region of the rabbit cardiac muscle Ca(2+) release channel (ryanodine receptor isoform 2). J Biol Chem 276(34): 31760–31771.

    Article  PubMed  CAS  Google Scholar 

  • Du GG, Imredy JP, MacLennan DH. 1998. Characterization of recombinant rabbit cardiac and skeletal muscle Ca2+ release channels (ryanodine receptors) with a novel [3H]ryanodine binding assay. J Biol Chem 273(50): 33259–33266.

    Article  PubMed  CAS  Google Scholar 

  • el-Hayek R, Lokuta AJ, Arevalo C, Valdivia HH. 1995. Peptide probe of ryanodine receptor function. Imperatoxin A, a peptide from the venom of the scorpion Pandinus imperator, selectively activates skeletal-type ryanodine receptor isoforms. J Biol Chem 270(48): 28696–28704.

    Article  PubMed  CAS  Google Scholar 

  • Finn BE, Evenas J, Drakenberg T, Waltho JP, Thulin E, et al. 1995. Calcium-induced structural changes and domain autonomy in calmodulin. Nat Struct Biol 2(9): 777–783.

    Article  PubMed  CAS  Google Scholar 

  • Fischer G, Wittmann-Liebold B, Lang K, Kiefhaber T, Schmid FX. 1989. Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins. Nature 337(6206): 476–478.

    Article  PubMed  CAS  Google Scholar 

  • Fisher JD, Krikler D, Hallidie-Smith KA. 1999. Familial polymorphic ventricular arrhythmias: A quarter century of successful medical treatment based on serial exercise-pharmacologic testing. J Am Coll Cardiol 34(7): 2015–2022.

    Article  PubMed  CAS  Google Scholar 

  • Frey N, McKinsey TA, Olson EN. 2000. Decoding calcium signals involved in cardiac growth and function. Nat Med 6(11): 1221–1227.

    Article  PubMed  CAS  Google Scholar 

  • Gaburjakova M, Gaburjakova J, Reiken S, Huang F, Marx SO, et al. 2001. FKBP12 binding modulates ryanodine receptor channel gating. J Biol Chem 276(20): 16931–16935.

    Article  PubMed  CAS  Google Scholar 

  • Galli L, Orrico A, Lorenzini S, Censini S, Falciani M, et al. 2006. Frequency and localization of mutations in the 106 exons of the RYR1 gene in 50 individuals with malignant hyperthermia. Hum Mutat 27(8): 830.

    Article  PubMed  Google Scholar 

  • Galvan DL, Borrego-Diaz E, Perez PJ, Mignery GA. 1999. Subunit oligomerization, and topology of the inositol 1,4, 5-trisphosphate receptor. J Biol Chem 274(41): 29483–29492.

    Article  PubMed  CAS  Google Scholar 

  • Gao L, Balshaw D, Xu L, Tripathy A, Xin C, et al. 2000. Evidence for a role of the lumenal M3-M4 loop in skeletal muscle Ca(2+) release channel (ryanodine receptor) activity and conductance. Biophys J 79(2): 828–840.

    Article  PubMed  CAS  Google Scholar 

  • George CH. 2008. Sarcoplasmic reticulum Ca2+ leak in heart failure: Mere observation or functional relevance?. Cardiovasc Res 77(2): 302–314.

    Article  PubMed  CAS  Google Scholar 

  • George CH, Yin CC, Lai FA. 2005. Toward a molecular understanding of the structure-function of ryanodine receptor Ca2+ release channels: Perspectives from recombinant expression systems. Cell Biochem Biophys 42(2): 197–222.

    Article  PubMed  CAS  Google Scholar 

  • Gerull B, Heuser A, Wichter T, Paul M, Basson CT, et al. 2004. Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy. Nat Genet 36(11): 1162–1164.

    Article  PubMed  CAS  Google Scholar 

  • Gibbs GM, Scanlon MJ, Swarbrick J, Curtis S, Gallant E, et al. 2006. The cysteine-rich secretory protein domain of Tpx-1 is related to ion channel toxins and regulates ryanodine receptor Ca2+ signaling. J Biol Chem 281(7): 4156–4163.

    Article  PubMed  CAS  Google Scholar 

  • Gillard EF, Otsu K, Fujii J, Khanna VK, de Leon S, et al. 1991. A substitution of cysteine for arginine 614 in the ryanodine receptor is potentially causative of human malignant hyperthermia. Genomics 11(3): 751–755.

    Article  PubMed  CAS  Google Scholar 

  • Grunwald R, Meissner G. 1995. Lumenal sites and C terminus accessibility of the skeletal muscle calcium release channel (ryanodine receptor). J Biol Chem 270(19): 11338–11347.

    Article  PubMed  CAS  Google Scholar 

  • Gurrola GB, Arevalo C, Sreekumar R, Lokuta AJ, Walker JW, et al. 1999. Activation of ryanodine receptors by imperatoxin A and a peptide segment of the II-III loop of the dihydropyridine receptor. J Biol Chem 274(12): 7879–7886.

    Article  PubMed  CAS  Google Scholar 

  • Harding MW, Galat A, Uehling DE, Schreiber SL. 1989. A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-prolyl isomerase. Nature 341(6244): 758–760.

    Article  PubMed  CAS  Google Scholar 

  • Horimoto M, Akino M, Takenaka T, Igarashi K, Inoue H, et al. 2000. Evolution of left ventricular involvement in arrhythmogenic right ventricular cardiomyopathy. Cardiology 93(3): 197–200.

    Article  PubMed  CAS  Google Scholar 

  • Ikemoto T, Iino M, Endo M. 1995. Enhancing effect of calmodulin on Ca(2+)-induced Ca2+ release in the sarcoplasmic reticulum of rabbit skeletal muscle fibres. J Physiol 487 (Pt 3): 573–582.

    PubMed  CAS  Google Scholar 

  • Jayaraman T, Brillantes AM, Timerman AP, Fleischer S, Erdjument-Bromage H, et al. 1992. FK506 binding protein associated with the calcium release channel (ryanodine receptor). J Biol Chem 267(14): 9474–9477.

    PubMed  CAS  Google Scholar 

  • Jiang Y, Lee A, Chen J, Cadene M, Chait BT, et al. 2002. The open pore conformation of potassium channels. Nature 417(6888): 523–526.

    Article  PubMed  CAS  Google Scholar 

  • Jones JL, Reynolds DF, Lai FA, Blayney LM. 2005. Ryanodine receptor binding to FKBP12 is modulated by channel activation state. J Cell Sci 118(Pt 20): 4613–4619.

    Article  PubMed  CAS  Google Scholar 

  • Jungbluth H. 2007. Central core disease. Orphanet J Rare Dis 2: 25.

    Article  PubMed  Google Scholar 

  • Kall L, Krogh A, Sonnhammer EL. 2004. A combined transmembrane topology and signal peptide prediction method. J Mol Biol 338(5): 1027–1036.

    Article  PubMed  CAS  Google Scholar 

  • Kino T, Hatanaka H, Hashimoto M, Nishiyama M, Goto T, et al. 1987. FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics. J Antibiot (Tokyo) 40(9): 1249–1255.

    CAS  Google Scholar 

  • Krogh A, Larsson B, von Heijne G, Sonnhammer EL. 2001. Predicting transmembrane protein topology with a hidden Markov model: Application to complete genomes. J Mol Biol 305(3): 567–580.

    Article  PubMed  CAS  Google Scholar 

  • Lai FA, Misra M, Xu L, Smith HA, Meissner G. 1989. The ryanodine receptor-Ca2+ release channel complex of skeletal muscle sarcoplasmic reticulum. Evidence for a cooperatively coupled, negatively charged homotetramer. J Biol Chem 264(28): 16776–16785.

    PubMed  CAS  Google Scholar 

  • Laitinen PJ, Brown KM, Piippo K, Swan H, Devaney JM, et al. 2001. Mutations of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia. Circulation 103(4): 485–490.

    PubMed  CAS  Google Scholar 

  • Laver DR. 2007. Ca2+ stores regulate ryanodine receptor Ca2+ release channels via luminal and cytosolic Ca2+ sites. Clin Exp Pharmacol Physiol 34(9): 889–896.

    Article  PubMed  CAS  Google Scholar 

  • Lee EH, Rho SH, Kwon SJ, Eom SH, Allen PD, et al. 2004. N-terminal region of FKBP12 is essential for binding to the skeletal ryanodine receptor. J Biol Chem 279(25): 26481–26488.

    Article  PubMed  CAS  Google Scholar 

  • Leissring MA, LaFerla FM, Callamaras N, Parker I. 2001. Subcellular mechanisms of presenilin-mediated enhancement of calcium signaling. Neurobiol Dis 8(3): 469–478.

    Article  PubMed  CAS  Google Scholar 

  • Leissring MA, Parker I, LaFerla FM. 1999a. Presenilin-2 mutations modulate amplitude and kinetics of inositol 1, 4,5-trisphosphate-mediated calcium signals. J Biol Chem 274(46): 32535–32538.

    Article  PubMed  CAS  Google Scholar 

  • Leissring MA, Paul BA, Parker I, Cotman CW, LaFerla FM. 1999b. Alzheimer’s presenilin-1 mutation potentiates inositol 1,4,5-trisphosphate-mediated calcium signaling in Xenopus oocytes. J Neurochem 72(3): 1061–1068.

    Article  PubMed  CAS  Google Scholar 

  • Liu Z, Zhang J, Li P, Chen SR, Wagenknecht T. 2002. Three-dimensional reconstruction of the recombinant type 2 ryanodine receptor and localization of its divergent region 1. J Biol Chem 277(48): 46712–46719.

    Article  PubMed  CAS  Google Scholar 

  • Liu Z, Zhang J, Wang R, Wayne Chen SR, Wagenknecht T. 2004. Location of divergent region 2 on the three-dimensional structure of cardiac muscle ryanodine receptor/calcium release channel. J Mol Biol 338(3): 533–545.

    Article  PubMed  CAS  Google Scholar 

  • Ludtke SJ, Serysheva II, Hamilton SL, Chiu W. 2005. The pore structure of the closed RyR1 channel. Structure 13(8): 1203–1211.

    Article  PubMed  CAS  Google Scholar 

  • Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. 2002. The protein kinase complement of the human genome. Science 298(5600): 1912–1934.

    Article  PubMed  CAS  Google Scholar 

  • Marcus FI, Fontaine GH, Guiraudon G, Frank R, Laurenceau JL, et al. 1982. Right ventricular dysplasia: A report of 24 adult cases. Circulation 65(2): 384–398.

    PubMed  CAS  Google Scholar 

  • Marx SO, Reiken S, Hisamatsu Y, Jayaraman T, Burkhoff D, et al. 2000. PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): Defective regulation in failing hearts. Cell 101(4): 365–376.

    Article  PubMed  CAS  Google Scholar 

  • Masumiya H, Wang R, Zhang J, Xiao B, Chen SR. 2003. Localization of the 12.6-kDa FK506-binding protein (FKBP12.6) binding site to the NH2-terminal domain of the cardiac Ca2+ release channel (ryanodine receptor). J Biol Chem 278(6): 3786–3792.

    Article  PubMed  CAS  Google Scholar 

  • Matadeen R, Patwardhan A, Gowen B, Orlova EV, Pape T, et al. 1999. The Escherichia coli large ribosomal subunit at 7.5 A resolution. Structure 7(12): 1575–1583.

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Meissner G. 1986. Evidence of a role for calmodulin in the regulation of calcium release from skeletal muscle sarcoplasmic reticulum. Biochemistry 25(1): 244–251.

    Article  PubMed  CAS  Google Scholar 

  • Meng X, Xiao B, Cai S, Huang X, Li F, et al. 2007. Three-dimensional localization of serine 2808, a phosphorylation site in cardiac ryanodine receptor. J Biol Chem 282(35): 25929–25939.

    Article  PubMed  CAS  Google Scholar 

  • Mitra K, Ubarretxena-Belandia I, Taguchi T, Warren G, Engelman DM. 2004. Modulation of the bilayer thickness of exocytic pathway membranes by membrane proteins rather than cholesterol. Proc Natl Acad Sci USA 101(12): 4083–4088.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Mygland A, Tysnes OB, Aarli JA, Matre R, Gilhus NE. 1993. IgG subclass distribution of ryanodine receptor autoantibodies in patients with myasthenia gravis and thymoma. J Autoimmun 6(4): 507–515.

    Article  PubMed  CAS  Google Scholar 

  • Nakata M, Kuwabara S, Kawaguchi N, Takahashi H, Misawa S, et al. 2007. Is excitation-contraction coupling impaired in myasthenia gravis?. Clin Neurophysiol 118(5): 1144–1148.

    Article  PubMed  Google Scholar 

  • O’Connell KM, Yamaguchi N, Meissner G, Dirksen RT. 2002. Calmodulin binding to the 3614–3643 region of RyR1 is not essential for excitation-contraction coupling in skeletal myotubes. J Gen Physiol 120(3): 337–347.

    Article  PubMed  Google Scholar 

  • Orlova EV, Serysheva II, van Heel M, Hamilton SL, Chiu W. 1996. Two structural configurations of the skeletal muscle calcium release channel. Nat Struct Biol 3(6): 547–552.

    Article  PubMed  CAS  Google Scholar 

  • Otsu K, Willard HF, Khanna VK, Zorzato F, Green NM, et al. 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.

    PubMed  CAS  Google Scholar 

  • Paolini C, Fessenden JD, Pessah IN, Franzini-Armstrong C. 2004a. Evidence for conformational coupling between two calcium channels. Proc Natl Acad Sci USA 101(34): 12748–12752.

    Article  PubMed  CAS  Google Scholar 

  • Paolini C, Protasi F, Franzini-Armstrong C. 2004b. The relative position of RyR feet and DHPR tetrads in skeletal muscle. J Mol Biol 342(1): 145–153.

    Article  PubMed  CAS  Google Scholar 

  • Pinna LA, Ruzzene M. 1996. How do protein kinases recognize their substrates?. Biochim Biophys Acta 1314(3): 191–225.

    Article  PubMed  CAS  Google Scholar 

  • Priori SG, Napolitano C, Tiso N, Memmi M, Vignati G, et al. 2001. Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation 103(2): 196–200.

    PubMed  CAS  Google Scholar 

  • Radermacher M. 1994. Three-dimensional reconstruction from random projections: Orientational alignment via Radon transforms. Ultramicroscopy 53(2): 121–136.

    Article  PubMed  CAS  Google Scholar 

  • Radermacher M, Rao V, Grassucci R, Frank J, Timerman AP, et al. 1994. Cryo-electron microscopy and three-dimensional reconstruction of the calcium release channel/ryanodine receptor from skeletal muscle. J Cell Biol 127(2): 411–423.

    Article  PubMed  CAS  Google Scholar 

  • Rampazzo A, Nava A, Malacrida S, Beffagna G, Bauce B, et al. 2002. Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet 71(5): 1200–1206.

    Article  PubMed  CAS  Google Scholar 

  • Ryazanov AG, Pavur KS, Dorovkov MV. 1999. Alpha-kinases: A new class of protein kinases with a novel catalytic domain. Curr Biol 9(2): R43–R45.

    Article  PubMed  CAS  Google Scholar 

  • Saibil HR. 2000. Macromolecular structure determination by cryo-electron microscopy. Acta Crystallogr D Biol Crystallogr 56(Pt 10): 1215–1222.

    Article  PubMed  CAS  Google Scholar 

  • Saito A, Inui M, Radermacher M, Frank J, Fleischer S. 1988. Ultrastructure of the calcium release channel of sarcoplasmic reticulum. J Cell Biol 107(1):211–219.

    Article  PubMed  CAS  Google Scholar 

  • Samso M, Shen X, Allen PD. 2006. Structural characterization of the RyR1-FKBP12 interaction. J Mol Biol 356(4): 917–927.

    Article  PubMed  CAS  Google Scholar 

  • Samso M, Trujillo R, Gurrola GB, Valdivia HH, Wagenknecht T. 1999. Three-dimensional location of the imperatoxin A binding site on the ryanodine receptor. J Cell Biol 146(2): 493–499.

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Samso M, Wagenknecht T, Allen PD. 2005. Internal structure and visualization of transmembrane domains of the RyR1 calcium release channel by cryo-EM. Nat Struct Mol Biol 12(6): 539–544.

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Schultz J, Milpetz F, Bork P, Ponting CP. 1998. SMART, a simple modular architecture research tool: Identification of signaling domains. Proc Natl Acad Sci USA 95(11): 5857–5864.

    Article  PubMed  CAS  Google Scholar 

  • Seiler S, Wegener AD, Whang DD, Hathaway DR, Jones LR. 1984. High molecular weight proteins in cardiac and skeletal muscle junctional sarcoplasmic reticulum vesicles bind calmodulin, are phosphorylated, and are degraded by Ca2+-activated protease. J Biol Chem 259(13): 8550–8557.

    PubMed  CAS  Google Scholar 

  • Serysheva II. 2004. Structural insights into excitation-contraction coupling by electron cryomicroscopy. Biochemistry (Mosc). 69(11): 1226–1232.

    Article  CAS  Google Scholar 

  • Serysheva II, Ludtke SJ, Baker ML, Cong Y, Topf M, et al. 2008. Subnanometer-resolution electron cryomicroscopy-based domain models for the cytoplasmic region of skeletal muscle RyR channel. Proc Natl Acad Sci USA 105(28): 9610–9615.

    Article  PubMed  Google Scholar 

  • Serysheva II, Orlova EV, Chiu W, Sherman MB, Hamilton SL, et al. 1995. Electron cryomicroscopy and angular reconstitution used to visualize the skeletal muscle calcium release channel. Nat Struct Biol 2(1): 18–24.

    Article  PubMed  CAS  Google Scholar 

  • Serysheva II, Schatz M, van Heel M, Chiu W, Hamilton SL. 1999. Structure of the skeletal muscle calcium release channel activated with Ca2+ and AMP-PCP. Biophys J 77(4): 1936–1944.

    Article  PubMed  CAS  Google Scholar 

  • Sharma MR, Jeyakumar LH, Fleischer S, Wagenknecht T. 2000. Three-dimensional structure of ryanodine receptor isoform three in two conformational states as visualized by cryo-electron microscopy. J Biol Chem 275(13): 9485–9491.

    Article  PubMed  CAS  Google Scholar 

  • Sharma MR, Jeyakumar LH, Fleischer S, Wagenknecht T. 2006. Three-dimensional visualization of FKBP12.6 binding to an open conformation of cardiac ryanodine receptor. Biophys J 90(1): 164–172.

    Article  PubMed  CAS  Google Scholar 

  • Sheridan DC, Takekura H, Franzini-Armstrong C, Beam KG, Allen PD, et al. 2006. Bidirectional signaling between calcium channels of skeletal muscle requires multiple direct and indirect interactions. Proc Natl Acad Sci USA 103(52): 19760–19765.

    Article  PubMed  CAS  Google Scholar 

  • Siekierka JJ, Hung SH, Poe M, Lin CS, Sigal NH. 1989a. A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin. Nature 341(6244): 755–757.

    Article  PubMed  CAS  Google Scholar 

  • Siekierka JJ, Staruch MJ, Hung SH, Sigal NH. 1989b. FK-506, a potent novel immunosuppressive agent, binds to a cytosolic protein which is distinct from the cyclosporin A-binding protein, cyclophilin. J Immunol 143(5): 1580–1583.

    PubMed  CAS  Google Scholar 

  • Song L, Alcalai R, Arad M, Wolf CM, Toka O, 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  PubMed  CAS  Google Scholar 

  • Sorrentino V, Volpe P. 1993. Ryanodine receptors: How many, where and why?. Trends Pharmacol Sci 14(3): 98–103.

    Article  PubMed  CAS  Google Scholar 

  • Stutzmann GE. 2007. The pathogenesis of Alzheimers disease is it a lifelong “calciumopathy”? Neuroscientist 13(5): 546–559.

    Article  PubMed  CAS  Google Scholar 

  • Stutzmann GE, Smith I, Caccamo A, Oddo S, Parker I, et al. 2007. Enhanced ryanodine-mediated calcium release in mutant PS1-expressing Alzheimer’s mouse models. Ann N Y Acad Sci 1097: 265–277.

    Article  PubMed  CAS  Google Scholar 

  • Swan H, Piippo K, Viitasalo M, Heikkila P, Paavonen T, et al. 1999. Arrhythmic disorder mapped to chromosome 1q42–q43 causes malignant polymorphic ventricular tachycardia in structurally normal hearts. J Am Coll Cardiol 34(7): 2035–2042.

    Article  PubMed  CAS  Google Scholar 

  • Takasago T, Imagawa T, Shigekawa M. 1989. Phosphorylation of the cardiac ryanodine receptor by cAMP-dependent protein kinase. J Biochem 106(5): 872–877.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Thiene G, Nava A, Corrado D, Rossi L, Pennelli N. 1988. Right ventricular cardiomyopathy and sudden death in young people. N Engl J Med 318(3): 129–133.

    PubMed  CAS  Google Scholar 

  • Thomas NL, George CH, Williams AJ, Lai FA. 2007. Ryanodine receptor mutations in arrhythmias: advances in understanding the mechanisms of channel dysfunction. Biochem Soc Trans 35(Pt 5): 946–951.

    Article  PubMed  CAS  Google Scholar 

  • Tiso N, Stephan DA, Nava A, Bagattin A, Devaney JM, et al. 2001. Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum Mol Genet 10(3): 189–194.

    Article  PubMed  CAS  Google Scholar 

  • Tripathy A, Resch W, Xu L, Valdivia HH, Meissner G. 1998. Imperatoxin A induces subconductance states in Ca2+ release channels (ryanodine receptors) of cardiac and skeletal muscle. J Gen Physiol 111(5): 679–690.

    Article  PubMed  CAS  Google Scholar 

  • Tunwell RE, Wickenden C, Bertrand BM, Shevchenko VI, Walsh MB, et al. 1996. The human cardiac muscle ryanodine receptor-calcium release channel: identification, primary structure and topological analysis. Biochem J 318(Pt 2): 477–487.

    PubMed  CAS  Google Scholar 

  • Van Acker K, Bultynck G, Rossi D, Sorrentino V, Boens N, et al. 2004. The 12 kDa FK506-binding protein, FKBP12, modulates the Ca(2+)-flux properties of the type-3 ryanodine receptor. J Cell Sci 117(Pt 7): 1129–1137.

    Article  PubMed  CAS  Google Scholar 

  • Velazquez-Campoy A, Leavitt SA, Freire E. 2004. Characterization of protein-protein interactions by isothermal titration calorimetry. Methods Mol Biol 261: 35–54.

    PubMed  CAS  Google Scholar 

  • Wagenknecht T, Berkowitz J, Grassucci R, Timerman AP, Fleischer S. 1994. Localization of calmodulin binding sites on the ryanodine receptor from skeletal muscle by electron microscopy. Biophys J 67(6): 2286–2295.

    Article  PubMed  CAS  Google Scholar 

  • Wagenknecht T, Radermacher M, Grassucci R, Berkowitz J, Xin HB, et al. 1997. Locations of calmodulin and FK506-binding protein on the three-dimensional architecture of the skeletal muscle ryanodine receptor. J Biol Chem 272(51): 32463–32471.

    Article  PubMed  CAS  Google Scholar 

  • Wang F, Li H, Liu MN, Song H, Han HM, et al. 2006. Structural and functional analysis of natrin, a venom protein that targets various ion channels. Biochem Biophys Res Commun 351(2): 443–448.

    Article  PubMed  CAS  Google Scholar 

  • Wang YL, Goh KX, Wu WG, Chen CJ. 2004. Purification, crystallization and preliminary X-ray crystallographic analysis of a cysteine-rich secretory protein (CRISP) from Naja atra venom. Acta Crystallogr D Biol Crystallogr 60(Pt 10): 1912–1915.

    Article  PubMed  CAS  Google Scholar 

  • Wehrens XH, Lehnart SE, Huang F, Vest JA, Reiken SR, et al. 2003. FKBP12.6 deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death. Cell 113(7): 829–840.

    Article  PubMed  CAS  Google Scholar 

  • Welch W, Rheault S, West DJ, Williams AJ. 2004. A model of the putative pore region of the cardiac ryanodine receptor channel. Biophys J 87(4): 2335–2351.

    Article  PubMed  CAS  Google Scholar 

  • Woo JS, Suh HY, Park SY, Oh BH. 2006. Structural basis for protein recognition by B30.2/SPRY domains. Mol Cell 24(6): 967–976.

    Article  PubMed  CAS  Google Scholar 

  • Xiao B, Sutherland C, Walsh MP, Chen SR. 2004. Protein kinase A phosphorylation at serine-2808 of the cardiac Ca2+-release channel (ryanodine receptor) does not dissociate 12.6-kDa FK506-binding protein (FKBP12.6). Circ Res 94(4): 487–495.

    Article  PubMed  CAS  Google Scholar 

  • Xin HB, Timerman AP, Onoue H, Wiederrecht GJ, Fleischer S. 1995. Affinity purification of the ryanodine receptor/calcium release channel from fast twitch skeletal muscle based on its tight association with FKBP12. Biochem Biophys Res Commun 214(1): 263–270.

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi N, Xu L, Pasek DA, Evans KE, Meissner G. 2003. Molecular basis of calmodulin binding to cardiac muscle Ca(2+) release channel (ryanodine receptor). J Biol Chem 278(26): 23480–23486.

    Article  PubMed  CAS  Google Scholar 

  • Yin CC, Blayney LM, Lai FA. 2005a. Physical coupling between ryanodine receptor-calcium release channels. J Mol Biol 349(3): 538–546.

    Article  PubMed  CAS  Google Scholar 

  • Yin CC, D'Cruz LG, Lai FA. 2008. Ryanodine receptor arrays: not just a pretty pattern? Trends Cell Biol. 18(4): 149–156.

    Article  PubMed  CAS  Google Scholar 

  • Yin CC, Han H, Wei R, Lai FA. 2005b. Two-dimensional crystallization of the ryanodine receptor Ca2+ release channel on lipid membranes. J Struct Biol 149(2): 219–224.

    Article  PubMed  CAS  Google Scholar 

  • Yin CC, Lai FA. 2000. Intrinsic lattice formation by the ryanodine receptor calcium-release channel. Nat Cell Biol 2(9): 669–671.

    Article  PubMed  CAS  Google Scholar 

  • Yoshikawa F, Morita M, Monkawa T, Michikawa T, Furuichi T, et al. 1996. Mutational analysis of the ligand binding site of the inositol 1,4,5-trisphosphate receptor. J Biol Chem 271(30): 18277–18284.

    Article  PubMed  CAS  Google Scholar 

  • Zhang J, Liu Z, Masumiya H, Wang R, Jiang D, et al. 2003. Three-dimensional localization of divergent region 3 of the ryanodine receptor to the clamp-shaped structures adjacent to the FKBP binding sites. J Biol Chem 278(16): 14211–14218.

    Article  PubMed  CAS  Google Scholar 

  • Zhang M, Tanaka T, Ikura M. 1995. Calcium-induced conformational transition revealed by the solution structure of apo calmodulin. Nat Struct Biol 2(9): 758–767.

    Article  PubMed  CAS  Google Scholar 

  • Zhao M, Li P, Li X, Zhang L, Winkfein RJ, et al. 1999. Molecular identification of the ryanodine receptor pore-forming segment. J Biol Chem 274(37): 25971–25974.

    Article  PubMed  CAS  Google Scholar 

  • Zhu X, Ghanta J, Walker JW, Allen PD, Valdivia HH. 2004. The calmodulin binding region of the skeletal ryanodine receptor acts as a self-modulatory domain. Cell Calcium 35(2): 165–177.

    Article  PubMed  CAS  Google Scholar 

  • Zissimopoulos S, Lai FA. 2005. Interaction of FKBP12.6 with the cardiac ryanodine receptor C-terminal domain. J Biol Chem 280(7): 5475–5485.

    Article  PubMed  CAS  Google Scholar 

  • Zorzato F, Fujii J, Otsu K, Phillips M, Green NM, 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.

    PubMed  CAS  Google Scholar 

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Acknowledgements

We Wish to thank the British Heart Foundation, European Commision, Medical Research Council and Wellcome Trust for supporting our research.

Authors
  1. L. G. D’Cruz
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  2. C. C. Yin
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  3. A. J. Williams
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  4. F. Anthony Lai
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 10962, 140 Old Orangeburg Road, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Group Director of Neuro-Developmental Disorder Research Group, RIKEN Brain Science Institute, 351-0198, 2-1 Hirosawa Wako-shi, Saitama, Japan

    Katsuhiko Mikoshiba

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D’Cruz, L.G., Yin, C.C., Williams, A.J., Anthony Lai, F. (2009). Insights into the Three-Dimensional Organization of Ryanodine Receptors. In: Lajtha, A., Mikoshiba, K. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30370-3_25

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