Skip to main content

Filamentous structures in skeletal muscle: anchors for the subsarcolemmal space

Abstract

In skeletal muscle fibers, intermediate filaments and actin filaments provide structural support to the myofibrils and the sarcolemma. For many years, it was poorly understood from ultrastructural observations that how these filamentous structures were kept anchored. The present study was conducted to determine the architecture of filamentous anchoring structures in the subsarcolemmal space and the intermyofibrils. The diaphragms (Dp) of adult wild type and mdx mice (mdx is a model for Duchenne muscular dystrophy) were subjected to tension applied perpendicular to the long axis of the muscle fibers, with or without treatment with 1 % Triton X-100 or 0.03 % saponin. These experiments were conducted to confirm the presence and integrity of the filamentous anchoring structures. Transmission electron microscopy revealed that these structures provide firm transverse connections between the sarcolemma and peripheral myofibrils. Most of the filamentous structures appeared to be inserted into subsarcolemmal densities, forming anchoring connections between the sarcolemma and peripheral myofibrils. In some cases, actin filaments were found to run longitudinally in the subsarcolemmal space to connect to the sarcolemma or in some cases to connect to the intermyofibrils as elongated thin filaments. These filamentous anchoring structures were less common in the mdx Dp. Our data suggest that the transverse and longitudinal filamentous structures form an anchoring system in the subsarcolemmal space and the intermyofibrils.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

References

  1. 1.

    Ramaekers FCS, Bosman FT (2004) The cytoskeleton and disease. J Pathol 204:351–354

    Article  CAS  PubMed  Google Scholar 

  2. 2.

    O’Neill A, Williams M, Resneck WG, Milner DJ, Capetanaki Y, Bloch RJ (2002) Sarcolemmal organization in skeletal muscle lacking desmin: evidence for cytokeratins associated with the membrane skeleton at costameres. Mol Biol Cell 13:2347–2359

    Article  PubMed Central  PubMed  Google Scholar 

  3. 3.

    Capetanaki Y, Bloch RJ, Kouloumenta A, Mavroidis M, Psarras S (2007) Muscle intermediate filaments and their links to membranes and membranous organelles. Exp Cell Res 313:2063–2076

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    Kee AJ, Gunning PW, Hardeman EC (2009) Diverse roles of the actin cytoskeleton in striated muscle. J Muscle Res Cell Motil 30:187–197

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Clark KA, McElhinny AS, Beckerle MC, Gregorio CC (2002) Striated muscle cytoarchitecture: an intricate web of form and function. Annu Rev Cell Dev Biol 18:637–706

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    Pardo JV, Siliciano JD, Craig SW (1983) A vinculin-containing cortical lattice in skeletal muscle: transverse lattice elements (“costameres”) mark sites of attachment between myofibrils and sarcolemma. Proc Natl Acad Sci USA 80:1008–1012

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. 7.

    Bloch RJ, Gonzales-Serratos H (2003) Lateral force transmission across costameres in skeletal muscle. Exerc Sport Sci Rev 31:73–78

    Article  PubMed  Google Scholar 

  8. 8.

    Ursitti JA, Lee PC, Resneck WG, McNally MM, Bowman AL, O’Neill A, Stone MR, Bloch RJ (2004) Cloning and characterization of cytokeratins 8 and 19 in adult rat striated muscle. Interaction with the dystrophin glycoprotein complex. J Biol Chem 279:41830–41838

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    Ervasti JM (2003) Costameres: the Achilles’ heel of herculean muscle. J Biol Chem 278:13591–13594

    Article  CAS  PubMed  Google Scholar 

  10. 10.

    Craig SW, Pardo JV (1983) Gamma actin, spectrin, and intermediate filament proteins colocalize with vinculin at costameres, myofibril-to-sarcolemma attachment sites. Cell Motil 3:449–462

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    Porter GA, Dmytrenko GM, Winkelmann JC, Bloch RJ (1992) Dystrophin colocalizes with β-spectrin in distinct subsarcolemmal domains in mammalian skeletal muscle. J Cell Biol 117:997–1005

    Article  CAS  PubMed  Google Scholar 

  12. 12.

    Stone MR, O’Neill A, Lovering RM, Strong J, Resneck WG, Reed PW, Toivola DM, Ursitti JA, Omary MB, Bloch RJ (2007) Absence of keratin 19 in mice causes skeletal myopathy with mitochondrial and sarcolemmal reorganization. J Cell Sci 120:3999–4008

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    Williams MW, Bloch RJ (1999) Extensive but coordinated reorganization of the membrane skeleton in myofibers of dystrophic (mdx) mice. J Cell Biol 144:1259–1270

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. 14.

    Williams MW, Resneck WG, Bloch RJ (2000) Membrane skeleton of innervated and denervated fast- and slow-twitch muscle. Muscle Nerve 23:590–599

    Article  CAS  PubMed  Google Scholar 

  15. 15.

    Williams MW, Resneck WG, Kaysser T, Ursitti JA, Birkenmeier CS, Barker JE, Bloch RJ (2001) Na, K-ATPase in skeletal muscle: two populations of β-spectrin control localization in the sarcolemma but not partitioning between the sarcolemma and the transverse tubules. J Cell Sci 114:751–762

    CAS  PubMed  Google Scholar 

  16. 16.

    Pierobon-Bormioli S (1981) Transverse sarcomere filamentous systems: “Z- and M-cables”. J Muscle Res Cell Motil 2:401–413

    Article  Google Scholar 

  17. 17.

    Bard F, Franzini-Armstrong C (1991) Extra actin filaments at the periphery of skeletal muscle myofibrils. Tissue Cell 23:191–197

    Article  CAS  PubMed  Google Scholar 

  18. 18.

    Hijikata T, Murakami T, Imamura M, Fujimaki N, Ishikawa H (1999) Plectin is a linker of intermediate filaments to Z-discs in skeletal muscle fibers. J Cell Sci 112:867–876

    CAS  PubMed  Google Scholar 

  19. 19.

    Street SF (1983) Lateral transmission of tension in frog myofibers: a myofibrillar network and transverse cytoskeletal connections are possible transmitters. J Cell Physiol 114:346–364

    Article  CAS  PubMed  Google Scholar 

  20. 20.

    Garamvölgyi N (1965) Inter-Z bridges in the flight muscle of the bee. J Ultrastruct Res 13:435–443

    Article  PubMed  Google Scholar 

  21. 21.

    Wang K, Ramirez-Mitchell R (1983) A network of transverse and longitudinal intermediate filaments is associated with sarcomeres of adult vertebrate skeletal muscle. J Cell Biol 96:562–570

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Shear CR, Bloch RJ (1985) Vinculin in subsarcolemmal densities in chicken skeletal muscle: localization and relationship to intracellular and extracellular structures. J Cell Biol 101:240–256

    Article  CAS  PubMed  Google Scholar 

  23. 23.

    Hijikata T, Murakami T, Ishikawa H, Yorifuji H (2003) Plectin tethers desmin intermediate filaments onto subsarcolemmal dense plaques containing dystrophin and vinculin. Histochem Cell Biol 119:109–123

    CAS  PubMed  Google Scholar 

  24. 24.

    Rybakova IN, Patel JR, Ervasti JM (2000) The dystrophin complex forms a mechanically strong link between the sarcolemma and costameric actin. J Cell Biol 150:1209–1214

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. 25.

    Hijikata T, Nakamura A, Isokawa K, Imamura M, Yuasa K, Ishikawa R, Kohama K, Takeda S, Yorifuji H (2008) Plectin 1 links intermediate filaments to costameric sarcolemma through β-synemin, α-dystrobrevin and actin. J Cell Sci 121:2062–2074

    Article  CAS  PubMed  Google Scholar 

  26. 26.

    Yorifuji H, Hirokawa N (1989) Cytoskeletal architecture of neuromuscular junction: localization of vinculin. J Electron Microsc Tech 12:160–171

    Article  CAS  PubMed  Google Scholar 

  27. 27.

    Stedman HH, Sweeney HL, Shrager JB, Maguire HC, Panettieri RA, Petrof B, Narusawa M, Leferovich JM, Sladky JT, Kelly AM (1991) The mdx mouse diaphragm reproduces the degenerative changes of Duchene muscular dystrophy. Nature 352:536–539

    Article  CAS  PubMed  Google Scholar 

  28. 28.

    Ishizaki M, Suga T, Kimura E, Shiota T, Kawano R, Uchida Y, Uchino K, Yamashita S, Maeda Y, Uchino M (2008) Mdx respiratory impairment following fibrosis of the diaphragm. Neuromuscul Disord 18:342–348

    Article  PubMed  Google Scholar 

  29. 29.

    Ishikawa H, Bischoff R, Holtzer H (1968) Mitosis and intermediate-sized filaments in developing skeletal muscle. J Cell Biol 38:538–555

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. 30.

    Cohen CM, Tyler JM, Branton D (1980) Spectrin-actin associations studied by electron microscopy of shadowed preparations. Cell 21:875–883

    Article  CAS  PubMed  Google Scholar 

  31. 31.

    Pons F, Augier N, Heilig R, Léger J, Mornet D, Léger JJ (1990) Isolated dystrophin molecules as seen by electron microscopy. Proc Natl Acad Sci USA 87:7851–7855

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. 32.

    Lazarides E (1980) Intermediate filaments as mechanical integrators of cellular space. Nature 283:249–256

    Article  CAS  PubMed  Google Scholar 

  33. 33.

    Straub V, Bittner RE, Léger JJ, Voit T (1992) Direct visualization of the dystrophin network on skeletal muscle fiber membrane. J Cell Biol 119:1183–1191

    Article  CAS  PubMed  Google Scholar 

  34. 34.

    Goldstein JA, McNally EM (2010) Mechanisms of muscle weakness in muscular dystrophy. J Gen Physiol 136:29–34

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. 35.

    Cullen MJ, Walsh J, Nicholson LVB, Harris JB (1990) Ultrastructural localization of dystrophin in human muscle by using gold immunolabelling. Proc R Soc Lond B Biol Sci 240:197–210

    Article  CAS  PubMed  Google Scholar 

  36. 36.

    Harris JB, Cullen MJ (1992) Ultrastructural localization and the possible role of dystrophin. In: Kalkulas BA, Howell JM, Roses AD (eds) Duchenne muscular dystrophy: animal models and genetic manipulation. Raven Press, New York, pp 19–40

    Google Scholar 

  37. 37.

    Stevenson SA, Cullen MJ, Rothery S, Coppen SR (2005) High-resolution en-face visualization of the cardiomyocyte plasma membrane reveals distinctive distributions of spectrin and dystrophin. Eur J Cell Biol 84:961–971

    Article  CAS  PubMed  Google Scholar 

  38. 38.

    Jung D, Yang B, Meyer J, Chamberlain JS, Campbell KP (1995) Identification and characterization of the dystrophin anchoring site on β-dystroglycan. J Biol Chem 270:27305–27310

    Article  CAS  PubMed  Google Scholar 

  39. 39.

    Ervasti JM, Campbell KP (1993) A role for the dystrophin-glycoprotein complex as a transmembrane linker between laminin and actin. J Cell Biol 122:809–823

    Article  CAS  PubMed  Google Scholar 

  40. 40.

    Ibraghimov-Beskrovnaya O, Ervasti JM, Leveille CJ, Slaughter CA, Sernett SW, Campbell KP (1992) Primary structure of dystrophin-associated glycoproteins linking dystrophin to extracellular matrix. Nature 355:696–702

    Article  CAS  PubMed  Google Scholar 

  41. 41.

    Hoffman EP, Kunkel LM (1989) Dystrophin abnormalities in Duchenne/Becker muscular dystrophy. Neuron 2:1019–1029

    Article  CAS  PubMed  Google Scholar 

  42. 42.

    Campbell KP (1995) Three muscular dystrophies: loss of cytoskeleton-extracellular matrix linkage. Cell 80:675–679

    Article  CAS  PubMed  Google Scholar 

  43. 43.

    O’Brien KF, Kunkel LM (2001) Dystrophin and muscular dystrophy: past, present, and future. Mol Genet Metab 74:75–88

    Article  PubMed  Google Scholar 

  44. 44.

    Law DJ, Allen DL, Tidball JG (1994) Talin, vinculin and DRP (utrophin) concentrations are increased at mdx myotendinous junctions following onset of necrosis. J Cell Sci 107:1477–1483

    CAS  PubMed  Google Scholar 

  45. 45.

    Bellin RM, Huiatt TW, Critchley DR, Robson RM (2001) Synemin may function to directly link muscle cell intermediate filaments to both myofibrillar Z-lines and costameres. J Biol Chem 276:32330–32337

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank H. Matsuda, M. Shikada and Y. Morimura for both technical and secretarial assistance. This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, KAKENHI Grant Numbers 20590183, 23590230.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Hiroshi Yorifuji.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Khairani, A.F., Tajika, Y., Takahashi, M. et al. Filamentous structures in skeletal muscle: anchors for the subsarcolemmal space. Med Mol Morphol 48, 1–12 (2015). https://doi.org/10.1007/s00795-014-0070-3

Download citation

Keywords

  • Cytoskeleton
  • Filamentous anchoring structure
  • Subsarcolemmal space
  • Costameres
  • Actin filament
  • Intermediate filament
  • Transmission electron microscopy