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. 1991 Jul 2;114(2):303–312. doi: 10.1083/jcb.114.2.303

The ryanodine receptor/junctional channel complex is regulated by growth factors in a myogenic cell line

PMCID: PMC2289071  PMID: 1649198

Abstract

The ryanodine receptor/junctional channel complex (JCC) forms the calcium release channel and foot structures of the sarcoplasmic reticulum. The JCC and the dihydropyridine (DHP) receptor in the transverse tubule are two of the major components involved in excitation-contraction (E-C) coupling in skeletal muscle. The DHP receptor is believed to serve as the voltage sensor in E-C coupling. Both the JCC and DHP receptor, as well as many skeletal muscle-specific contractile protein genes, are expressed in the BC3H1 muscle cell line. In the present study, we find that during differentiation of BC3H1 cells, induced by mitogen withdrawal, induction of the JCC and DHP receptor mRNAs is temporally similar to that of the skeletal muscle contractile protein genes alpha-tropomyosin and alpha-actin. Our data suggest that there is coordinate regulation of both the contractile protein genes (which have been studied in detail previously) and the genes encoding the calcium channels involved in E-C coupling. Induction of both calcium channels is accompanied by profound changes in BC3H1 cell morphology including the development of many components of mature skeletal muscle cells, despite lack of myoblast fusion. Visualized by electron microscopy, the JCC appears as "foot structures" located in the dyad junction between the plasmalemma and the sarcoplasmic reticulum of the BC3H1 cells. Development of foot structures is concomitant with JCC mRNA expression. Expression of the JCC and DHP receptor mRNAs and formation of the foot structures are inhibited specifically by fibroblast growth factor.

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Selected References

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  1. Brennan T. J., Edmondson D. G., Olson E. N. Aberrant regulation of MyoD1 contributes to the partially defective myogenic phenotype of BC3H1 cells. J Cell Biol. 1990 Apr;110(4):929–937. doi: 10.1083/jcb.110.4.929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Caffrey J. M., Brown A. M., Schneider M. D. Mitogens and oncogenes can block the induction of specific voltage-gated ion channels. Science. 1987 May 1;236(4801):570–573. doi: 10.1126/science.2437651. [DOI] [PubMed] [Google Scholar]
  3. Clegg C. H., Linkhart T. A., Olwin B. B., Hauschka S. D. Growth factor control of skeletal muscle differentiation: commitment to terminal differentiation occurs in G1 phase and is repressed by fibroblast growth factor. J Cell Biol. 1987 Aug;105(2):949–956. doi: 10.1083/jcb.105.2.949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Coughlin S. R., Lee W. M., Williams P. W., Giels G. M., Williams L. T. c-myc gene expression is stimulated by agents that activate protein kinase C and does not account for the mitogenic effect of PDGF. Cell. 1985 Nov;43(1):243–251. doi: 10.1016/0092-8674(85)90029-7. [DOI] [PubMed] [Google Scholar]
  5. Devlin R. B., Emerson C. P., Jr Coordinate regulation of contractile protein synthesis during myoblast differentiation. Cell. 1978 Apr;13(4):599–611. doi: 10.1016/0092-8674(78)90211-8. [DOI] [PubMed] [Google Scholar]
  6. Endo T., Nadal-Ginard B. Three types of muscle-specific gene expression in fusion-blocked rat skeletal muscle cells: translational control in EGTA-treated cells. Cell. 1987 May 22;49(4):515–526. doi: 10.1016/0092-8674(87)90454-5. [DOI] [PubMed] [Google Scholar]
  7. Fleischer S., Inui M. Biochemistry and biophysics of excitation-contraction coupling. Annu Rev Biophys Biophys Chem. 1989;18:333–364. doi: 10.1146/annurev.bb.18.060189.002001. [DOI] [PubMed] [Google Scholar]
  8. Fornwald J. A., Kuncio G., Peng I., Ordahl C. P. The complete nucleotide sequence of the chick a-actin gene and its evolutionary relationship to the actin gene family. Nucleic Acids Res. 1982 Jul 10;10(13):3861–3876. doi: 10.1093/nar/10.13.3861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Franzini-Armstrong C., Nunzi G. Junctional feet and particles in the triads of a fast-twitch muscle fibre. J Muscle Res Cell Motil. 1983 Apr;4(2):233–252. doi: 10.1007/BF00712033. [DOI] [PubMed] [Google Scholar]
  10. Hymel L., Inui M., Fleischer S., Schindler H. Purified ryanodine receptor of skeletal muscle sarcoplasmic reticulum forms Ca2+-activated oligomeric Ca2+ channels in planar bilayers. Proc Natl Acad Sci U S A. 1988 Jan;85(2):441–445. doi: 10.1073/pnas.85.2.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Konieczny S. F., Drobes B. L., Menke S. L., Taparowsky E. J. Inhibition of myogenic differentiation by the H-ras oncogene is associated with the down regulation of the MyoD1 gene. Oncogene. 1989 Apr;4(4):473–481. [PubMed] [Google Scholar]
  12. Lai F. A., Erickson H. P., Rousseau E., Liu Q. Y., Meissner G. Purification and reconstitution of the calcium release channel from skeletal muscle. Nature. 1988 Jan 28;331(6154):315–319. doi: 10.1038/331315a0. [DOI] [PubMed] [Google Scholar]
  13. Lathrop B., Olson E., Glaser L. Control by fibroblast growth factor of differentiation in the BC3H1 muscle cell line. J Cell Biol. 1985 May;100(5):1540–1547. doi: 10.1083/jcb.100.5.1540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Marks A. R., Tempst P., Chadwick C. C., Riviere L., Fleischer S., Nadal-Ginard B. Smooth muscle and brain inositol 1,4,5-trisphosphate receptors are structurally and functionally similar. J Biol Chem. 1990 Dec 5;265(34):20719–20722. [PubMed] [Google Scholar]
  15. Marks A. R., Tempst P., Hwang K. S., Taubman M. B., Inui M., Chadwick C., Fleischer S., Nadal-Ginard B. Molecular cloning and characterization of the ryanodine receptor/junctional channel complex cDNA from skeletal muscle sarcoplasmic reticulum. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8683–8687. doi: 10.1073/pnas.86.22.8683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Munson R., Jr, Caldwell K. L., Glaser L. Multiple controls for the synthesis of muscle-specific proteins in BC3H1 cells. J Cell Biol. 1982 Feb;92(2):350–356. doi: 10.1083/jcb.92.2.350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Olson E. N., Caldwell K. L., Gordon J. I., Glaser L. Regulation of creatine phosphokinase expression during differentiation of BC3H1 cells. J Biol Chem. 1983 Feb 25;258(4):2644–2652. [PubMed] [Google Scholar]
  18. Olson E. N., Glaser L., Merlie J. P., Lindstrom J. Expression of acetylcholine receptor alpha-subunit mRNA during differentiation of the BC3H1 muscle cell line. J Biol Chem. 1984 Mar 10;259(5):3330–3336. [PubMed] [Google Scholar]
  19. 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]
  20. Rios E., Brum G. Involvement of dihydropyridine receptors in excitation-contraction coupling in skeletal muscle. Nature. 1987 Feb 19;325(6106):717–720. doi: 10.1038/325717a0. [DOI] [PubMed] [Google Scholar]
  21. Ruiz-Opazo N., Weinberger J., Nadal-Ginard B. Comparison of alpha-tropomyosin sequences from smooth and striated muscle. Nature. 1985 May 2;315(6014):67–70. doi: 10.1038/315067a0. [DOI] [PubMed] [Google Scholar]
  22. Saito A., Inui M., Radermacher M., Frank J., Fleischer S. Ultrastructure of the calcium release channel of sarcoplasmic reticulum. J Cell Biol. 1988 Jul;107(1):211–219. doi: 10.1083/jcb.107.1.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Saito A., Wang C. T., Fleischer S. Membrane asymmetry and enhanced ultrastructural detail of sarcoplasmic reticulum revealed with use of tannic acid. J Cell Biol. 1978 Dec;79(3):601–616. doi: 10.1083/jcb.79.3.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schneider M. D., Perryman M. B., Payne P. A., Spizz G., Roberts R., Olson E. N. Autonomous expression of c-myc in BC3H1 cells partially inhibits but does not prevent myogenic differentiation. Mol Cell Biol. 1987 May;7(5):1973–1977. doi: 10.1128/mcb.7.5.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schubert D., Harris A. J., Devine C. E., Heinemann S. Characterization of a unique muscle cell line. J Cell Biol. 1974 May;61(2):398–413. doi: 10.1083/jcb.61.2.398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Smith J. S., Imagawa T., Ma J., Fill M., Campbell K. P., Coronado R. Purified ryanodine receptor from rabbit skeletal muscle is the calcium-release channel of sarcoplasmic reticulum. J Gen Physiol. 1988 Jul;92(1):1–26. doi: 10.1085/jgp.92.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Standaert M. L., Schimmel S. D., Pollet R. J. The development of insulin receptors and responses in the differentiating nonfusing muscle cell line BC3H-1. J Biol Chem. 1984 Feb 25;259(4):2337–2345. [PubMed] [Google Scholar]
  28. Strauch A. R., Offord J. D., Chalkley R., Rubenstein P. A. Characterization of actin mRNA levels during BC3H1 cell differentiation. J Biol Chem. 1986 Jan 15;261(2):849–855. [PubMed] [Google Scholar]
  29. 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]
  30. Tanabe T., Beam K. G., Powell J. A., Numa S. Restoration of excitation-contraction coupling and slow calcium current in dysgenic muscle by dihydropyridine receptor complementary DNA. Nature. 1988 Nov 10;336(6195):134–139. doi: 10.1038/336134a0. [DOI] [PubMed] [Google Scholar]
  31. Tanabe T., Takeshima H., Mikami A., Flockerzi V., Takahashi H., Kangawa K., Kojima M., Matsuo H., Hirose T., Numa S. Primary structure of the receptor for calcium channel blockers from skeletal muscle. Nature. 1987 Jul 23;328(6128):313–318. doi: 10.1038/328313a0. [DOI] [PubMed] [Google Scholar]
  32. Taubman M. B., Smith C. W., Izumo S., Grant J. W., Endo T., Andreadis A., Nadal-Ginard B. The expression of sarcomeric muscle-specific contractile protein genes in BC3H1 cells: BC3H1 cells resemble skeletal myoblasts that are defective for commitment to terminal differentiation. J Cell Biol. 1989 May;108(5):1799–1806. doi: 10.1083/jcb.108.5.1799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Vaidya T. B., Rhodes S. J., Taparowsky E. J., Konieczny S. F. Fibroblast growth factor and transforming growth factor beta repress transcription of the myogenic regulatory gene MyoD1. Mol Cell Biol. 1989 Aug;9(8):3576–3579. doi: 10.1128/mcb.9.8.3576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wagenknecht T., Grassucci R., Frank J., Saito A., Inui M., Fleischer S. Three-dimensional architecture of the calcium channel/foot structure of sarcoplasmic reticulum. Nature. 1989 Mar 9;338(6211):167–170. doi: 10.1038/338167a0. [DOI] [PubMed] [Google Scholar]
  35. Wice B., Milbrandt J., Glaser L. Control of muscle differentiation in BC3H1 cells by fibroblast growth factor and vanadate. J Biol Chem. 1987 Feb 5;262(4):1810–1817. [PubMed] [Google Scholar]
  36. Wieczorek D. F., Smith C. W., Nadal-Ginard B. The rat alpha-tropomyosin gene generates a minimum of six different mRNAs coding for striated, smooth, and nonmuscle isoforms by alternative splicing. Mol Cell Biol. 1988 Feb;8(2):679–694. doi: 10.1128/mcb.8.2.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. 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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