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A physiological role for titin and nebulin in skeletal muscle

Nature volume 323, pages 160–164 (1986)Cite this article

Abstract

Production of active force in skeletal muscle results from the interaction of myosin-containing thick filaments with actiri-containing thin filaments. These muscles are also passively elastic, producing forces that resist stretch independently of ATP splitting or of interaction between the filaments. The mechanism of this passive elasticity is unknown; suggestions include gap filaments in the region between thick and thin filaments in muscles stretched beyond filament overlap1–5, or intermediate filaments which connect successive Z-disks6. Recently, the two exceptionally large proteins titin (also called connectin) and nebulin (originally called band 3) have been implicated in passive elasticity (for review see refs 7, 8). Here, we show that after these proteins are degraded by low doses of ionizing radiation, the ability of single skinned muscle cells to generate both passive tension in response to stretch and active tension in response to calcium is greatly reduced. These effects are accompanied by axial misalignment of thick filaments. Titin and/or nebulin apparently provide axial continuity for the production of resting tension on stretch and also tend to keep the thick filaments centred within the sarcomere during force generation.

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References

  1. Carlsen F., Knappeis, G. G. & Buchthal, F. J. biophys. biochem. Cytol. 11, 95–117 (1961).

    Article  CAS  Google Scholar 

  2. Huxley, A. F. & Peachey, L. D. J. Physiol., Lond. 156, 150–165 (1961).

    Article  CAS  Google Scholar 

  3. Locker, R. H. & Leet, N. G. J. Ultrastruct. Res. 52, 64–75 (1975).

    Article  CAS  Google Scholar 

  4. Magid, A., Ting-Beall, H. P., Carvell, M., Kontis, T. & Lucaveche, C. in Contractile Mechanisms in Muscle (eds Pollack, G. H. & Sugi, H.) 307–328 (Plenum, New York, 1984).

    Book  Google Scholar 

  5. Sjostrand, F. S. J. Ultrastruct. Res. 7, 225–246 (1962).

    Article  CAS  Google Scholar 

  6. Wang, K. & Ramirez-Mitchell, R. J. Cell Biol. 96, 562–570 (1983).

    Article  CAS  Google Scholar 

  7. Maruyama, K. in Muscle Contraction: Its Regulatory Mechanisms (eds Ebashi, S., Maruyama, K. & Endo, M.) 485–496 (Springer, New York, 1980).

    Google Scholar 

  8. Wang, K. Cell Muscle Motil. 6, 315–369 (1985).

    Article  CAS  Google Scholar 

  9. Maruyama, K., Kimura, S., Yoshidomi, H., Sawada, H. & Kikuchi, M. J. Biochem., Tokyo 95, 1423–1433 (1984).

    Article  CAS  Google Scholar 

  10. Wang, K. & Williamson, C. L. Proc. natn. Acad. Sci. U.S.A. 77, 3254–3258 (1980).

    Article  ADS  CAS  Google Scholar 

  11. Maruyama, K., Kimura, S., Ohashi, K. & Kuwano, Y. J. Biochem., Tokyo 89, 701–709 (1981).

    Article  CAS  Google Scholar 

  12. Wang, K., Wright, J. & Ramirez-Mitchell, R. Biophys. J. 47, 349a (1985).

    Article  Google Scholar 

  13. Wang, K., McClure, J. & Tu, A. Proc. natn. Acad. Sci. U.S.A. 76, 3698–3702 (1979).

    Article  ADS  CAS  Google Scholar 

  14. Kempner, E. S. & Haigler, H. T. in Growth and Maturation Factors Vol. 3 (ed. Guroff, G.) 149–173 (Wiley, New York, 1985).

    Google Scholar 

  15. Kempner, E. S. & Haigler, H. T. J. biol. Chem. 257, 13297–13299 (1982).

    CAS  PubMed  Google Scholar 

  16. Magid, A. & Law, D. J. Science 230, 1280–1282 (1985).

    Article  ADS  CAS  Google Scholar 

  17. Podolsky, R. J. J. Physiol., Lond. 170, 110–123 (1964).

    Article  CAS  Google Scholar 

  18. Mannherz, H. G. & Goody, R. S. A. Rev. Biochem. 45, 427–465 (1976).

    Article  CAS  Google Scholar 

  19. Hanson, J., O'Brien, E. J. & Bennett, P. M. J. molec. Biol. 58, 865–871 (1971).

    Article  CAS  Google Scholar 

  20. Atwood, K. C. & Norman, A. Proc. natn. Acad. Sci. U.S.A 35, 696–709 (1949).

    Article  ADS  CAS  Google Scholar 

  21. Maruyama, K., Yoshioka, T., Higuchi, H., Ohashi, K., Kimura, S. & Natori, R. J. Cell Biol. 101, 2167–2172 (1985).

    Article  CAS  Google Scholar 

  22. Trinick, J., Knight, P. & Whiting, A. J. molec. Biol. 180, 331–356 (1984).

    Article  CAS  Google Scholar 

  23. Higuchi, H. & Umazume, Y. Biophys. J. 48, 137–147 (1985).

    Article  ADS  CAS  Google Scholar 

  24. Maruyama, K., Sawada, H., Kimura, S., Ohashi, K., Higuchi, H. & Umazume, Y. J. Cell Biol. 99, 1391–1397 (1984).

    Article  CAS  Google Scholar 

  25. Wood, D. S., Zollman, J., Rueben, J. P. & Brandt, P. W. Science 187, 1075–1076 (1975).

    Article  ADS  CAS  Google Scholar 

  26. Somerville, L. L. & Wang, K. Biochem. biophys. Res. Commun. 102, 53–58 (1981).

    Article  CAS  Google Scholar 

  27. Thames, M. D., Teichholz, L. E. & Podolsky, R. J. J. gen. PhysioL 63, 509–530 (1974).

    Article  CAS  Google Scholar 

  28. Goldman, Y. E. & Simmons, R. M. J. PhysioL, Lond. 350, 497–518 (1984).

    Article  CAS  Google Scholar 

  29. Hellam, D. C. & Podolsky, R. J. J. PhysioL, Lond. 200, 807–819 (1969).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, 20892, USA

    Robert Horowits & Richard J. Podolsky

  2. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 20892, USA

    Ellis S. Kempner & Margaret E. Bisher

Authors
  1. Robert Horowits
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  2. Ellis S. Kempner
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  3. Margaret E. Bisher
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  4. Richard J. Podolsky
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Horowits, R., Kempner, E., Bisher, M. et al. A physiological role for titin and nebulin in skeletal muscle. Nature 323, 160–164 (1986). https://doi.org/10.1038/323160a0

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