Skip to main content
Biophysical Journal logoLink to Biophysical Journal
. 2002 Jun;82(6):3144–3149. doi: 10.1016/S0006-3495(02)75656-7

Morphology and molecular composition of sarcoplasmic reticulum surface junctions in the absence of DHPR and RyR in mouse skeletal muscle.

Edward Felder 1, Feliciano Protasi 1, Ronit Hirsch 1, Clara Franzini-Armstrong 1, Paul D Allen 1
PMCID: PMC1302103  PMID: 12023238

Abstract

Calcium release during excitation-contraction coupling of skeletal muscle cells is initiated by the functional interaction of the exterior membrane and the sarcoplasmic reticulum (SR), mediated by the "mechanical" coupling of ryanodine receptors (RyR) and dihydropyridine receptors (DHPR). RyR is the sarcoplasmic reticulum Ca(2+) release channel and DHPR is an L-type calcium channel of exterior membranes (surface membrane and T tubules), which acts as the voltage sensor of excitation-contraction coupling. The two proteins communicate with each other at junctions between SR and exterior membranes called calcium release units and are associated with several proteins of which triadin and calsequestrin are the best characterized. Calcium release units are present in diaphragm muscles and hind limb derived primary cultures of double knock out mice lacking both DHPR and RyR. The junctions show coupling between exterior membranes and SR, and an apparently normal content and disposition of triadin and calsequestrin. Therefore SR-surface docking, targeting of triadin and calsequestrin to the junctional SR domains and the structural organization of the two latter proteins are not affected by lack of DHPR and RyR. Interestingly, simultaneous lack of the two major excitation-contraction coupling proteins results in decrease of calcium release units frequency in the diaphragm, compared with either single knockout mutation.

Full Text

The Full Text of this article is available as a PDF (475.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams B. A., Tanabe T., Mikami A., Numa S., Beam K. G. Intramembrane charge movement restored in dysgenic skeletal muscle by injection of dihydropyridine receptor cDNAs. Nature. 1990 Aug 9;346(6284):569–572. doi: 10.1038/346569a0. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Beam K. G., Knudson C. M., Powell J. A. A lethal mutation in mice eliminates the slow calcium current in skeletal muscle cells. Nature. 1986 Mar 13;320(6058):168–170. doi: 10.1038/320168a0. [DOI] [PubMed] [Google Scholar]
  4. Buck E. D., Nguyen H. T., Pessah I. N., Allen P. D. Dyspedic mouse skeletal muscle expresses major elements of the triadic junction but lacks detectable ryanodine receptor protein and function. J Biol Chem. 1997 Mar 14;272(11):7360–7367. doi: 10.1074/jbc.272.11.7360. [DOI] [PubMed] [Google Scholar]
  5. Caswell A. H., Brandt N. R., Brunschwig J. P., Purkerson S. Localization and partial characterization of the oligomeric disulfide-linked molecular weight 95,000 protein (triadin) which binds the ryanodine and dihydropyridine receptors in skeletal muscle triadic vesicles. Biochemistry. 1991 Jul 30;30(30):7507–7513. doi: 10.1021/bi00244a020. [DOI] [PubMed] [Google Scholar]
  6. Caswell A. H., Brunschwig J. P. Identification and extraction of proteins that compose the triad junction of skeletal muscle. J Cell Biol. 1984 Sep;99(3):929–939. doi: 10.1083/jcb.99.3.929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chaudhari N., Beam K. G. mRNA for cardiac calcium channel is expressed during development of skeletal muscle. Dev Biol. 1993 Feb;155(2):507–515. doi: 10.1006/dbio.1993.1048. [DOI] [PubMed] [Google Scholar]
  8. Costello B., Chadwick C., Saito A., Chu A., Maurer A., Fleischer S. Characterization of the junctional face membrane from terminal cisternae of sarcoplasmic reticulum. J Cell Biol. 1986 Sep;103(3):741–753. doi: 10.1083/jcb.103.3.741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Flucher B. E., Andrews S. B., Fleischer S., Marks A. R., Caswell A., Powell J. A. Triad formation: organization and function of the sarcoplasmic reticulum calcium release channel and triadin in normal and dysgenic muscle in vitro. J Cell Biol. 1993 Dec;123(5):1161–1174. doi: 10.1083/jcb.123.5.1161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Flucher B. E., Franzini-Armstrong C. Formation of junctions involved in excitation-contraction coupling in skeletal and cardiac muscle. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):8101–8106. doi: 10.1073/pnas.93.15.8101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Franzini-Armstrong C., Kenney L. J., Varriano-Marston E. The structure of calsequestrin in triads of vertebrate skeletal muscle: a deep-etch study. J Cell Biol. 1987 Jul;105(1):49–56. doi: 10.1083/jcb.105.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Franzini-Armstrong C., Pincon-Raymond M., Rieger F. Muscle fibers from dysgenic mouse in vivo lack a surface component of peripheral couplings. Dev Biol. 1991 Aug;146(2):364–376. doi: 10.1016/0012-1606(91)90238-x. [DOI] [PubMed] [Google Scholar]
  13. Franzini-Armstrong C., Protasi F. Ryanodine receptors of striated muscles: a complex channel capable of multiple interactions. Physiol Rev. 1997 Jul;77(3):699–729. doi: 10.1152/physrev.1997.77.3.699. [DOI] [PubMed] [Google Scholar]
  14. Houenou L. J., Pinçon-Raymond M., Garcia L., Harris A. J., Rieger F. Neuromuscular development following tetrodotoxin-induced inactivity in mouse embryos. J Neurobiol. 1990 Dec;21(8):1249–1261. doi: 10.1002/neu.480210809. [DOI] [PubMed] [Google Scholar]
  15. Ito K., Komazaki S., Sasamoto K., Yoshida M., Nishi M., Kitamura K., Takeshima H. Deficiency of triad junction and contraction in mutant skeletal muscle lacking junctophilin type 1. J Cell Biol. 2001 Sep 3;154(5):1059–1067. doi: 10.1083/jcb.200105040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jones L. R., Suzuki Y. J., Wang W., Kobayashi Y. M., Ramesh V., Franzini-Armstrong C., Cleemann L., Morad M. Regulation of Ca2+ signaling in transgenic mouse cardiac myocytes overexpressing calsequestrin. J Clin Invest. 1998 Apr 1;101(7):1385–1393. doi: 10.1172/JCI1362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jorgensen A. O., Shen A. C., Campbell K. P., MacLennan D. H. Ultrastructural localization of calsequestrin in rat skeletal muscle by immunoferritin labeling of ultrathin frozen sections. J Cell Biol. 1983 Nov;97(5 Pt 1):1573–1581. doi: 10.1083/jcb.97.5.1573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Knudson C. M., Chaudhari N., Sharp A. H., Powell J. A., Beam K. G., Campbell K. P. Specific absence of the alpha 1 subunit of the dihydropyridine receptor in mice with muscular dysgenesis. J Biol Chem. 1989 Jan 25;264(3):1345–1348. [PubMed] [Google Scholar]
  19. Luo Z. D., Pincon-Raymond M., Taylor P. Acetylcholinesterase and nicotinic acetylcholine receptor expression diverge in muscular dysgenic mice lacking the L-type calcium channel. J Neurochem. 1996 Jul;67(1):111–118. doi: 10.1046/j.1471-4159.1996.67010111.x. [DOI] [PubMed] [Google Scholar]
  20. Meissner G. Isolation and characterization of two types of sarcoplasmic reticulum vesicles. Biochim Biophys Acta. 1975 Apr 21;389(1):51–68. doi: 10.1016/0005-2736(75)90385-5. [DOI] [PubMed] [Google Scholar]
  21. Morton M. E., Froehner S. C. Monoclonal antibody identifies a 200-kDa subunit of the dihydropyridine-sensitive calcium channel. J Biol Chem. 1987 Sep 5;262(25):11904–11907. [PubMed] [Google Scholar]
  22. Nori A., Gola E., Tosato S., Cantini M., Volpe P. Targeting of calsequestrin to sarcoplasmic reticulum after deletions of its acidic carboxy terminus. Am J Physiol. 1999 Nov;277(5 Pt 1):C974–C981. doi: 10.1152/ajpcell.1999.277.5.C974. [DOI] [PubMed] [Google Scholar]
  23. Protasi F., Franzini-Armstrong C., Allen P. D. Role of ryanodine receptors in the assembly of calcium release units in skeletal muscle. J Cell Biol. 1998 Feb 23;140(4):831–842. doi: 10.1083/jcb.140.4.831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Protasi F., Franzini-Armstrong C., Flucher B. E. Coordinated incorporation of skeletal muscle dihydropyridine receptors and ryanodine receptors in peripheral couplings of BC3H1 cells. J Cell Biol. 1997 May 19;137(4):859–870. doi: 10.1083/jcb.137.4.859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Protasi F., Sun X. H., Franzini-Armstrong C. Formation and maturation of the calcium release apparatus in developing and adult avian myocardium. Dev Biol. 1996 Jan 10;173(1):265–278. doi: 10.1006/dbio.1996.0022. [DOI] [PubMed] [Google Scholar]
  26. Protasi F., Takekura H., Wang Y., Chen S. R., Meissner G., Allen P. D., Franzini-Armstrong C. RYR1 and RYR3 have different roles in the assembly of calcium release units of skeletal muscle. Biophys J. 2000 Nov;79(5):2494–2508. doi: 10.1016/S0006-3495(00)76491-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rando T. A., Blau H. M. Primary mouse myoblast purification, characterization, and transplantation for cell-mediated gene therapy. J Cell Biol. 1994 Jun;125(6):1275–1287. doi: 10.1083/jcb.125.6.1275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Richler C., Yaffe D. The in vitro cultivation and differentiation capacities of myogenic cell lines. Dev Biol. 1970 Sep;23(1):1–22. doi: 10.1016/s0012-1606(70)80004-5. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Schneider M. F., Chandler W. K. Voltage dependent charge movement of skeletal muscle: a possible step in excitation-contraction coupling. Nature. 1973 Mar 23;242(5395):244–246. doi: 10.1038/242244a0. [DOI] [PubMed] [Google Scholar]
  31. Stern M. D., Pizarro G., Ríos E. Local control model of excitation-contraction coupling in skeletal muscle. J Gen Physiol. 1997 Oct;110(4):415–440. doi: 10.1085/jgp.110.4.415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Takekura H., Flucher B. E., Franzini-Armstrong C. Sequential docking, molecular differentiation, and positioning of T-Tubule/SR junctions in developing mouse skeletal muscle. Dev Biol. 2001 Nov 15;239(2):204–214. doi: 10.1006/dbio.2001.0437. [DOI] [PubMed] [Google Scholar]
  33. Takekura H., Franzini-Armstrong C. Correct targeting of dihydropyridine receptors and triadin in dyspedic mouse skeletal muscle in vivo. Dev Dyn. 1999 Apr;214(4):372–380. doi: 10.1002/(SICI)1097-0177(199904)214:4<372::AID-AJA9>3.0.CO;2-Q. [DOI] [PubMed] [Google Scholar]
  34. Takekura H., Nishi M., Noda T., Takeshima H., Franzini-Armstrong C. Abnormal junctions between surface membrane and sarcoplasmic reticulum in skeletal muscle with a mutation targeted to the ryanodine receptor. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3381–3385. doi: 10.1073/pnas.92.8.3381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. 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]
  36. Takeshima H., Komazaki S., Nishi M., Iino M., Kangawa K. Junctophilins: a novel family of junctional membrane complex proteins. Mol Cell. 2000 Jul;6(1):11–22. doi: 10.1016/s1097-2765(00)00003-4. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Tanabe T., Beam K. G., Adams B. A., Niidome T., Numa S. Regions of the skeletal muscle dihydropyridine receptor critical for excitation-contraction coupling. Nature. 1990 Aug 9;346(6284):567–569. doi: 10.1038/346567a0. [DOI] [PubMed] [Google Scholar]
  39. Zhang L., Franzini-Armstrong C., Ramesh V., Jones L. R. Structural alterations in cardiac calcium release units resulting from overexpression of junctin. J Mol Cell Cardiol. 2001 Feb;33(2):233–247. doi: 10.1006/jmcc.2000.1295. [DOI] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES