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. 1996 Apr 1;315(Pt 1):207–216. doi: 10.1042/bj3150207

Alpha and beta isoforms of ryanodine receptor from chicken skeletal muscle are the homologues of mammalian RyR1 and RyR3.

L Ottini 1, G Marziali 1, A Conti 1, A Charlesworth 1, V Sorrentino 1
PMCID: PMC1217172  PMID: 8670108

Abstract

To define the relationship between the two ryanodine receptor (RyR) isoforms present in chicken skeletal muscle, we cloned two groups of cDNAs encoding the chicken homologues of mammalian RyR1 and RyR3. Equivalent amounts of the two chicken isoform mRNAs were detected in thigh and pectoral skeletal muscles. RyR1 and RyR3 mRNAs were co-expressed in testis and cerebellum whereas RyR3 mRNA was expressed also in the cerebrum and heart. The full-length sequence of the chicken RyR3 cDNA was established. The RyR3 receptor from chicken had the same general structure as mammalian and amphibian RyRs. The 15089 nt cDNA encoded a 4869-amino-acid-long protein with a molecular mass of 552445. The predicted amino acid sequence of the chicken RyR3 showed 86.9% identity to mammalian RyR3 and 85.6% to frog RyR3. Antibodies specific for chicken RyR1 and RyR3 recognized two different proteins with an apparent molecular mass of about 500 kDa. The two proteins differ slightly in their apparent molecular mass on SDS/PAGE: the protein recognized by antibodies against RyR3 had a higher mobility than the protein recognized by the antiserum against RyR1. Antibodies against RyR1 detected a protein already present in chicken skeletal muscle from 12-day-old embryos and older, while antibodies against RyR3 isoform detected a protein in muscle from only 18-day-old embryos and older. The expression patterns of RyR1 and RyR3 superimpose with those previously reported for the alpha and beta isoforms respectively. We conclude that alpha and beta isoforms present in chicken skeletal muscle are the homologues of mammalian RyR1 and RyR3.

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Selected References

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  1. Airey J. A., Baring M. D., Beck C. F., Chelliah Y., Deerinck T. J., Ellisman M. H., Houenou L. J., McKemy D. D., Sutko J. L., Talvenheimo J. Failure to make normal alpha ryanodine receptor is an early event associated with the crooked neck dwarf (cn) mutation in chicken. Dev Dyn. 1993 Jul;197(3):169–188. doi: 10.1002/aja.1001970303. [DOI] [PubMed] [Google Scholar]
  2. Airey J. A., Baring M. D., Sutko J. L. Ryanodine receptor protein is expressed during differentiation in the muscle cell lines BC3H1 and C2C12. Dev Biol. 1991 Nov;148(1):365–374. doi: 10.1016/0012-1606(91)90344-3. [DOI] [PubMed] [Google Scholar]
  3. Airey J. A., Beck C. F., Murakami K., Tanksley S. J., Deerinck T. J., Ellisman M. H., Sutko J. L. Identification and localization of two triad junctional foot protein isoforms in mature avian fast twitch skeletal muscle. J Biol Chem. 1990 Aug 25;265(24):14187–14194. [PubMed] [Google Scholar]
  4. Airey J. A., Deerinck T. J., Ellisman M. H., Houenou L. J., Ivanenko A., Kenyon J. L., McKemy D. D., Sutko J. L. Crooked neck dwarf (cn) mutant chicken skeletal muscle cells in low density primary cultures fail to express normal alpha ryanodine receptor and exhibit a partial mutant phenotype. Dev Dyn. 1993 Jul;197(3):189–202. doi: 10.1002/aja.1001970304. [DOI] [PubMed] [Google Scholar]
  5. Airey J. A., Grinsell M. M., Jones L. R., Sutko J. L., Witcher D. Three ryanodine receptor isoforms exist in avian striated muscles. Biochemistry. 1993 Jun 8;32(22):5739–5745. doi: 10.1021/bi00073a003. [DOI] [PubMed] [Google Scholar]
  6. Block B. A., Imagawa T., Campbell K. P., Franzini-Armstrong C. Structural evidence for direct interaction between the molecular components of the transverse tubule/sarcoplasmic reticulum junction in skeletal muscle. J Cell Biol. 1988 Dec;107(6 Pt 2):2587–2600. doi: 10.1083/jcb.107.6.2587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bull R., Marengo J. J. Sarcoplasmic reticulum release channels from frog skeletal muscle display two types of calcium dependence. FEBS Lett. 1993 Oct 4;331(3):223–227. doi: 10.1016/0014-5793(93)80341-q. [DOI] [PubMed] [Google Scholar]
  8. Callaway C., Seryshev A., Wang J. P., Slavik K. J., Needleman D. H., Cantu C., 3rd, Wu Y., Jayaraman T., Marks A. R., Hamilton S. L. Localization of the high and low affinity [3H]ryanodine binding sites on the skeletal muscle Ca2+ release channel. J Biol Chem. 1994 Jun 3;269(22):15876–15884. [PubMed] [Google Scholar]
  9. Catterall W. A. Excitation-contraction coupling in vertebrate skeletal muscle: a tale of two calcium channels. Cell. 1991 Mar 8;64(5):871–874. doi: 10.1016/0092-8674(91)90309-m. [DOI] [PubMed] [Google Scholar]
  10. Chadwick C. C., Saito A., Fleischer S. Isolation and characterization of the inositol trisphosphate receptor from smooth muscle. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2132–2136. doi: 10.1073/pnas.87.6.2132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Chen S. R., Airey J. A., MacLennan D. H. Positioning of major tryptic fragments in the Ca2+ release channel (ryanodine receptor) resulting from partial digestion of rabbit skeletal muscle sarcoplasmic reticulum. J Biol Chem. 1993 Oct 25;268(30):22642–22649. [PubMed] [Google Scholar]
  12. Chen S. R., MacLennan D. H. Identification of calmodulin-, Ca(2+)-, and ruthenium red-binding domains in the Ca2+ release channel (ryanodine receptor) of rabbit skeletal muscle sarcoplasmic reticulum. J Biol Chem. 1994 Sep 9;269(36):22698–22704. [PubMed] [Google Scholar]
  13. Chen S. R., Zhang L., MacLennan D. H. Antibodies as probes for Ca2+ activation sites in the Ca2+ release channel (ryanodine receptor) of rabbit skeletal muscle sarcoplasmic reticulum. J Biol Chem. 1993 Jun 25;268(18):13414–13421. [PubMed] [Google Scholar]
  14. Chen S. R., Zhang L., MacLennan D. H. Characterization of a Ca2+ binding and regulatory site in the Ca2+ release channel (ryanodine receptor) of rabbit skeletal muscle sarcoplasmic reticulum. J Biol Chem. 1992 Nov 15;267(32):23318–23326. [PubMed] [Google Scholar]
  15. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  16. Ellisman M. H., Deerinck T. J., Ouyang Y., Beck C. F., Tanksley S. J., Walton P. D., Airey J. A., Sutko J. L. Identification and localization of ryanodine binding proteins in the avian central nervous system. Neuron. 1990 Aug;5(2):135–146. doi: 10.1016/0896-6273(90)90304-x. [DOI] [PubMed] [Google Scholar]
  17. Franzini-Armstrong C., Jorgensen A. O. Structure and development of E-C coupling units in skeletal muscle. Annu Rev Physiol. 1994;56:509–534. doi: 10.1146/annurev.ph.56.030194.002453. [DOI] [PubMed] [Google Scholar]
  18. Furuichi T., Furutama D., Hakamata Y., Nakai J., Takeshima H., Mikoshiba K. Multiple types of ryanodine receptor/Ca2+ release channels are differentially expressed in rabbit brain. J Neurosci. 1994 Aug;14(8):4794–4805. doi: 10.1523/JNEUROSCI.14-08-04794.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Giannini G., Clementi E., Ceci R., Marziali G., Sorrentino V. Expression of a ryanodine receptor-Ca2+ channel that is regulated by TGF-beta. Science. 1992 Jul 3;257(5066):91–94. doi: 10.1126/science.1320290. [DOI] [PubMed] [Google Scholar]
  20. Giannini G., Conti A., Mammarella S., Scrobogna M., Sorrentino V. The ryanodine receptor/calcium channel genes are widely and differentially expressed in murine brain and peripheral tissues. J Cell Biol. 1995 Mar;128(5):893–904. doi: 10.1083/jcb.128.5.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. González A., Ríos E. Perchlorate enhances transmission in skeletal muscle excitation-contraction coupling. J Gen Physiol. 1993 Sep;102(3):373–421. doi: 10.1085/jgp.102.3.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gorza L., Vettore S., Volpe P., Sorrentino V., Samuel J. L., Anger M., Lompré A. M. Cardiac myocytes differ in mRNA composition for sarcoplasmic reticulum Ca2+ channels and Ca2+ pumps. Ann N Y Acad Sci. 1995 Mar 27;752:141–148. doi: 10.1111/j.1749-6632.1995.tb17417.x. [DOI] [PubMed] [Google Scholar]
  23. Hakamata Y., Nakai J., Takeshima H., Imoto K. Primary structure and distribution of a novel ryanodine receptor/calcium release channel from rabbit brain. FEBS Lett. 1992 Nov 9;312(2-3):229–235. doi: 10.1016/0014-5793(92)80941-9. [DOI] [PubMed] [Google Scholar]
  24. Ivanenko A., McKemy D. D., Kenyon J. L., Airey J. A., Sutko J. L. Embryonic chicken skeletal muscle cells fail to develop normal excitation-contraction coupling in the absence of the alpha ryanodine receptor. Implications for a two-ryanodine receptor system. J Biol Chem. 1995 Mar 3;270(9):4220–4223. doi: 10.1074/jbc.270.9.4220. [DOI] [PubMed] [Google Scholar]
  25. Jacquemond V., Csernoch L., Klein M. G., Schneider M. F. Voltage-gated and calcium-gated calcium release during depolarization of skeletal muscle fibers. Biophys J. 1991 Oct;60(4):867–873. doi: 10.1016/S0006-3495(91)82120-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lai F. A., Liu Q. Y., Xu L., el-Hashem A., Kramarcy N. R., Sealock R., Meissner G. Amphibian ryanodine receptor isoforms are related to those of mammalian skeletal or cardiac muscle. Am J Physiol. 1992 Aug;263(2 Pt 1):C365–C372. doi: 10.1152/ajpcell.1992.263.2.C365. [DOI] [PubMed] [Google Scholar]
  27. Lu X., Xu L., Meissner G. Activation of the skeletal muscle calcium release channel by a cytoplasmic loop of the dihydropyridine receptor. J Biol Chem. 1994 Mar 4;269(9):6511–6516. [PubMed] [Google Scholar]
  28. Ma J., Anderson K., Shirokov R., Levis R., González A., Karhanek M., Hosey M. M., Meissner G., Ríos E. Effects of perchlorate on the molecules of excitation-contraction coupling of skeletal and cardiac muscle. J Gen Physiol. 1993 Sep;102(3):423–448. doi: 10.1085/jgp.102.3.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Marty I., Robert M., Villaz M., De Jongh K., Lai Y., Catterall W. A., Ronjat M. Biochemical evidence for a complex involving dihydropyridine receptor and ryanodine receptor in triad junctions of skeletal muscle. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2270–2274. doi: 10.1073/pnas.91.6.2270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mattei M. G., Giannini G., Moscatelli F., Sorrentino V. Chromosomal localization of murine ryanodine receptor genes RYR1, RYR2, and RYR3 by in situ hybridization. Genomics. 1994 Jul 1;22(1):202–204. doi: 10.1006/geno.1994.1362. [DOI] [PubMed] [Google Scholar]
  31. McPherson P. S., Campbell K. P. Characterization of the major brain form of the ryanodine receptor/Ca2+ release channel. J Biol Chem. 1993 Sep 15;268(26):19785–19790. [PubMed] [Google Scholar]
  32. Meissner G. Ryanodine receptor/Ca2+ release channels and their regulation by endogenous effectors. Annu Rev Physiol. 1994;56:485–508. doi: 10.1146/annurev.ph.56.030194.002413. [DOI] [PubMed] [Google Scholar]
  33. Nakai J., Imagawa T., Hakamat Y., Shigekawa M., Takeshima H., Numa S. Primary structure and functional expression from cDNA of the cardiac ryanodine receptor/calcium release channel. FEBS Lett. 1990 Oct 1;271(1-2):169–177. doi: 10.1016/0014-5793(90)80399-4. [DOI] [PubMed] [Google Scholar]
  34. O'Brien J., Meissner G., Block B. A. The fastest contracting muscles of nonmammalian vertebrates express only one isoform of the ryanodine receptor. Biophys J. 1993 Dec;65(6):2418–2427. doi: 10.1016/S0006-3495(93)81303-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. O'Brien J., Valdivia H. H., Block B. A. Physiological differences between the alpha and beta ryanodine receptors of fish skeletal muscle. Biophys J. 1995 Feb;68(2):471–482. doi: 10.1016/S0006-3495(95)80208-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Olivares E. B., Tanksley S. J., Airey J. A., Beck C. F., Ouyang Y., Deerinck T. J., Ellisman M. H., Sutko J. L. Nonmammalian vertebrate skeletal muscles express two triad junctional foot protein isoforms. Biophys J. 1991 Jun;59(6):1153–1163. doi: 10.1016/S0006-3495(91)82331-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Otsu K., Willard H. F., Khanna V. K., Zorzato F., Green N. M., MacLennan D. H. Molecular cloning of cDNA encoding the Ca2+ release channel (ryanodine receptor) of rabbit cardiac muscle sarcoplasmic reticulum. J Biol Chem. 1990 Aug 15;265(23):13472–13483. [PubMed] [Google Scholar]
  38. Ouyang Y., Deerinck T. J., Walton P. D., Airey J. A., Sutko J. L., Ellisman M. H. Distribution of ryanodine receptors in the chicken central nervous system. Brain Res. 1993 Aug 27;620(2):269–280. doi: 10.1016/0006-8993(93)90165-j. [DOI] [PubMed] [Google Scholar]
  39. Oyamada H., Murayama T., Takagi T., Iino M., Iwabe N., Miyata T., Ogawa Y., Endo M. Primary structure and distribution of ryanodine-binding protein isoforms of the bullfrog skeletal muscle. J Biol Chem. 1994 Jun 24;269(25):17206–17214. [PubMed] [Google Scholar]
  40. Percival A. L., Williams A. J., Kenyon J. L., Grinsell M. M., Airey J. A., Sutko J. L. Chicken skeletal muscle ryanodine receptor isoforms: ion channel properties. Biophys J. 1994 Nov;67(5):1834–1850. doi: 10.1016/S0006-3495(94)80665-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Persson B., Argos P. Prediction of transmembrane segments in proteins utilising multiple sequence alignments. J Mol Biol. 1994 Mar 25;237(2):182–192. doi: 10.1006/jmbi.1994.1220. [DOI] [PubMed] [Google Scholar]
  42. Ríos E., Pizarro G., Stefani E. Charge movement and the nature of signal transduction in skeletal muscle excitation-contraction coupling. Annu Rev Physiol. 1992;54:109–133. doi: 10.1146/annurev.ph.54.030192.000545. [DOI] [PubMed] [Google Scholar]
  43. Ríos E., Pizarro G. Voltage sensor of excitation-contraction coupling in skeletal muscle. Physiol Rev. 1991 Jul;71(3):849–908. doi: 10.1152/physrev.1991.71.3.849. [DOI] [PubMed] [Google Scholar]
  44. Schneider M. F. Control of calcium release in functioning skeletal muscle fibers. Annu Rev Physiol. 1994;56:463–484. doi: 10.1146/annurev.ph.56.030194.002335. [DOI] [PubMed] [Google Scholar]
  45. Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
  46. Sorrentino V., Giannini G., Malzac P., Mattei M. G. Localization of a novel ryanodine receptor gene (RYR3) to human chromosome 15q14-q15 by in situ hybridization. Genomics. 1993 Oct;18(1):163–165. doi: 10.1006/geno.1993.1446. [DOI] [PubMed] [Google Scholar]
  47. Sorrentino V. The ryanodine receptor family of intracellular calcium release channels. Adv Pharmacol. 1995;33:67–90. doi: 10.1016/s1054-3589(08)60666-3. [DOI] [PubMed] [Google Scholar]
  48. Sorrentino V., Volpe P. Ryanodine receptors: how many, where and why? Trends Pharmacol Sci. 1993 Mar;14(3):98–103. doi: 10.1016/0165-6147(93)90072-r. [DOI] [PubMed] [Google Scholar]
  49. Sutko J. L., Airey J. A., Murakami K., Takeda M., Beck C., Deerinck T., Ellisman M. H. Foot protein isoforms are expressed at different times during embryonic chick skeletal muscle development. J Cell Biol. 1991 May;113(4):793–803. doi: 10.1083/jcb.113.4.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Takeshima H., Iino M., Takekura H., Nishi M., Kuno J., Minowa O., Takano H., Noda T. Excitation-contraction uncoupling and muscular degeneration in mice lacking functional skeletal muscle ryanodine-receptor gene. Nature. 1994 Jun 16;369(6481):556–559. doi: 10.1038/369556a0. [DOI] [PubMed] [Google Scholar]
  51. Takeshima H., Nishi M., Iwabe N., Miyata T., Hosoya T., Masai I., Hotta Y. Isolation and characterization of a gene for a ryanodine receptor/calcium release channel in Drosophila melanogaster. FEBS Lett. 1994 Jan 3;337(1):81–87. doi: 10.1016/0014-5793(94)80634-9. [DOI] [PubMed] [Google Scholar]
  52. Takeshima H., Nishimura S., Matsumoto T., Ishida H., Kangawa K., Minamino N., Matsuo H., Ueda M., Hanaoka M., Hirose T. Primary structure and expression from complementary DNA of skeletal muscle ryanodine receptor. Nature. 1989 Jun 8;339(6224):439–445. doi: 10.1038/339439a0. [DOI] [PubMed] [Google Scholar]
  53. Takeshima H., Yamazawa T., Ikemoto T., Takekura H., Nishi M., Noda T., Iino M. Ca(2+)-induced Ca2+ release in myocytes from dyspedic mice lacking the type-1 ryanodine receptor. EMBO J. 1995 Jul 3;14(13):2999–3006. doi: 10.1002/j.1460-2075.1995.tb07302.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Walton P. D., Airey J. A., Sutko J. L., Beck C. F., Mignery G. A., Südhof T. C., Deerinck T. J., Ellisman M. H. Ryanodine and inositol trisphosphate receptors coexist in avian cerebellar Purkinje neurons. J Cell Biol. 1991 Jun;113(5):1145–1157. doi: 10.1083/jcb.113.5.1145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Zorzato F., Fujii J., Otsu K., Phillips M., Green N. M., Lai F. A., Meissner G., MacLennan D. H. Molecular cloning of cDNA encoding human and rabbit forms of the Ca2+ release channel (ryanodine receptor) of skeletal muscle sarcoplasmic reticulum. J Biol Chem. 1990 Feb 5;265(4):2244–2256. [PubMed] [Google Scholar]

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