Letter | Published:

Immunoelectron microscopic localization of dystrophin in myofibres

Abstract

Duchenne muscular dystrophy, a common X-linked recessive human disease, has recently been shown to be caused by the deficiency of a large, low abundance protein called 'dystrophin'1–2. Biochemical techniques have shown dystrophin to be membrane-associated in skeletal muscle3, with enrichment of dystrophin in the t-tubules of 'triads'3,4. Other studies using immunohistochemistry on thick (10 μm) sections have shown dystrophin to be located at the periphery of muscle fibres, possibly at the plasma membrane5–7. These results have been interpreted as being either consistent and complementary6, or contradictory7. To localize dystrophin more precisely relative to these membrane systems we have employed highly sensitive and spatially accurate immuno-gold electron microscopy of ultra-thin (70–100 nm) cryosections. The major distribution of dystrophin was on the cytoplasmic face of the plasma membrane of muscle fibres, and possibly on the contiguous t-tubule membranes. The presented data, taken together with recently accumulated information regarding the primary structure of dystrophin8, suggests that dystrophin is a component of the membrane cytoskeleton in myogenic cells. Thus, myofibre necrosis in patients affected with Duchenne muscular dystrophy is likely the result of plasma membrane instability.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Hoffman, E. P., Brown, R. H. & Kunkel, L. M. Cell 51, 919–928 (1987).

  2. 2

    Hoffman, E. P. et al. New Engl. J. Med. 318, 1363–1368 (1988).

  3. 3

    Hoffman, E. P., Knudson, C. M., Campbell, K. P. & Kunkel, L. M. Nature 330, 754–758 (1987).

  4. 4

    Knudson, C. M., Hoffman, E. P., Kahl, S. D., Kunkel, L. M. & Campbell, K. P. J. biol. Chem. (in the press).

  5. 5

    Sugita, H. et al. Proc. Japan Acad. 64, 37–39.

  6. 6

    Bonilla, E. et al. Cell (in the press).

  7. 7

    Zubrzycka-Gaarn, E. E. et al. Nature 333, 466–469 (1988).

  8. 8

    Koenig, M., Monaco, A. P. & Kunkel, L. M. Cell 53, 219–228 (1988).

  9. 9

    Hammond, R. G. Cell 51, 1 (1987).

  10. 10

    Davison, M. D. & Critchley, D. R. Cell 52, 159–160 (1988).

  11. 11

    Bullfield, G., Siller, W. G., Wight, P. A. & Moore, K. J. Proc. Natn. Acad. Sci. U.S.A. 81, 1189–92 (1984).

  12. 12

    Hoffman, E. H., Hudecki, M. S., Rosenberg, P. A., Pollina, C. M. & Kunkel, L. M. Neuron (in the press).

  13. 13

    Eisenberg, B. R. in Handbook of Physiology, Section 10: Skeletal Muscle (ed. Peachy, L.D.) 73–112 (American Physiological Society, Bethesda, 1983).

  14. 14

    Lazarides, E. Cell 51, 345–356 (1987).

  15. 15

    Lazarides, E. & Capetanaki, Y. G. in Molecular Biology of Muscle Development (eds Emerson, C., Fischman, D., Nadal-Ginard, B. & Siddiqui, M. A. Q.) 749–772 (Alan R. Liss, New York, 1986).

  16. 16

    Rowland, L. P. Muscle Nerve 3, 3–20 (1980).

  17. 17

    Lotz, B. P. & F.ngel, A. G. Neurology 37, 1466–75 (1987).

  18. 18

    Cullen, M. J. & Mastaglia, F. L. Br. Med. Bull. 36, 145–152 (1980).

  19. 19

    Engel, A. G. in Myology: Basic and Clinical (ed. Engle, A. G. & Banker, B. Q.) 1185–1240 (McGraw-Hill, New York, 1986).

  20. 20

    Watkins, S. C., Samuel, J. L., Marotte, F., Bertier-Savalle, B. & Rappaport, L. Circ. Res. 60, 327–336 (1987).

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.