Acta Neuropathologica

, Volume 83, Issue 2, pp 158–169

The distribution of desmin and titin in normal and dystrophic human muscle

Authors

  • M. J. Cullen
    • University School of Neuroscience
    • Muscular Dystrophy Group Laboratories, Regional Neurosciences CentreNewcastle General Hospital
  • J. J. Fulthorpe
    • University School of Neuroscience
    • Muscular Dystrophy Group Laboratories, Regional Neurosciences CentreNewcastle General Hospital
  • J. B. Harris
    • University School of Neuroscience
    • Muscular Dystrophy Group Laboratories, Regional Neurosciences CentreNewcastle General Hospital
Regular Papers

DOI: 10.1007/BF00308475

Cite this article as:
Cullen, M.J., Fulthorpe, J.J. & Harris, J.B. Acta Neuropathol (1992) 83: 158. doi:10.1007/BF00308475

Summary

We have used monoclonal antibodies to desmin and titin, and a combination of immunofluoescence and immunogold labelling to study the disposition of these two proteins in normal human muscle fibres and in fibres at various stages of degeneration in dystrophic muscle. The normal pattern of desmin labelling, in particular the subsarcolemmal labelling, became disrupted at an early stage of fibre breakdown. There was a change from a transverse to a longitudinal orientation of the labelled intermediate filaments as the myofibrils sheared relative to one another. Thus, while it is probable that the desmin filaments are able to play a role in the mechanical integration of the myofibrils in healthy muscle, our results suggest that they cannot withstand the excessive forces generated by the hypercontraction and stretching of dystrophic muscle. However, small accumulations of desmin persisted between the damaged myofibrils until necrosis reached an advanced stage. In general, the degradation of titin appeared to occur before the degradation of desmin, and at the ultrastructural level, labelling with antibodies to epitopes from parts of the titin molecule close to the A-I-band junction was lost before labelling with an antibody to an epitope in the A-band. This suggests that different regions of the titin molecule break down at different stages in the breakdown of the fibre. We propose that lysis of titin in the I-band may underlie ‘slippage’, an abnormality often seen in dystrophic muscle, in which the A-band slips to one pole of the sarcomere such that it abuts onto the Z-line. Breakdown of the A-band section of titin may facilitate the disassembly of the A-filaments.

Key words

Skeletal muscleMuscular dystrophyTitinDesmin

Copyright information

© Springer-Verlag 1992