How to build a myofibril

  • Joseph W. SangerEmail author
  • Songman Kang
  • Cornelia C. Siebrands
  • Nancy Freeman
  • Aiping Du
  • Jushuo Wang
  • Andrea L. Stout
  • Jean M. Sanger


Building a myofibril from its component proteins requires the interactions of many different proteins in a process whose details are not understood. Several models have been proposed to provide a framework for understanding the increasing data on new myofibrillar proteins and their localizations during muscle development. In this article we discuss four current models that seek to explain how the assembly occurs in vertebrate cross-striated muscles. The models hypothesize: (a) stress fiber-like structures as templates for the assembly of myofibrils, (b) assembly in which the actin filaments and Z-bands form subunits independently from A-band subunits, with the two subsequently joined together to form a myofibril, (c) premyofibrils as precursors of myofibrils, or (d) assembly occurring without any intermediary structures. The premyofibril model, proposed by the authors, is discussed in more detail as it could explain myofibrillogenesis under a variety of different conditions: in ovo, in explants, and in tissue culture studies on cardiac and skeletal muscles.


Taxol Skeletal Muscle Cell Cardiac Muscle Cell Nebulin Nonmuscle Myosin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors are indebted to Ms. Victoria McManus for her comments on this manuscript. This work was supported by grants from AHA (JMS), MDA (JWS, JMS), and the National Institutes of Health (JWS, JMS); AHA fellowship (AD).


  1. Almenar-Queralt A, Gregorio CC, Fowler VM, (1999) Tropomodulin assembles early in myofibrillogenesis in chick skeletal muscle: evidence that thin filaments rearrange to form striated myofibrils J Cell Sci 112:1111–1123PubMedGoogle Scholar
  2. Antin PB, Forry-Schaudies S, Friedman TM, Tapscott SJ, Holtzer H, (1981) Taxol induces postmitotic myoblasts to assemble interdigitating microtubule-myosin arrays that exclude actin filaments J Cell Biol 90: 300–308CrossRefPubMedGoogle Scholar
  3. Ayoob JC, Shaner NC, Sanger JM, Sanger JW, (2001) Expression of Green or Red Fluorescent Protein (GFP or DsRed) linked proteins in Non-muscle and Muscle Cells Mol Biotechnol 17: 65–71CrossRefPubMedGoogle Scholar
  4. Buxton DB, Golomb E, Adelstein RS, (2003) Induction of nonmuscle myosin heavy chain II-C by butyrate in RAW 264.7 mouse macrophages J Cell Biol 278: 15449–15455Google Scholar
  5. Chowrashi P, Mittal B, Sanger JM, Sanger JW, (2002) Amorphin is phosphorylase; phosphorylase is an alpha-actinin-binding protein Cell Motil Cytoskeleton 53: 125–135CrossRefPubMedGoogle Scholar
  6. Clark KA, McElhinny AS, Beckerle MC, Gregorio CC, (2002) Striated muscle cytoarchitecture: an intricate web of form and function Ann Rev Cell Dev Biol 18: 637–706CrossRefGoogle Scholar
  7. Claycomb WC, Palazzo MC, (1980) Culture of the terminally differentiated adult cardiac muscle cell: a light and scanning electron microscope study Dev Biol 80: 466–482PubMedGoogle Scholar
  8. Conrad AH, Jaffredo T, Conrad GW, (1995) Differential localization of cytoplasmic myosin II isoforms A and B in avian interphase and dividing embryonic and immortalized cardiomyocytes and other cell types in vitro Cell Motil Cytoskeleton 31: 93–112CrossRefPubMedGoogle Scholar
  9. Costa ML, Escaleira RC, Rodrigues VB, Manasfi M, Mermelstein CS, (2002) Some distinctive features of zebrafish myogenesis based on unexpected distributions of the muscle cytoskeletal proteins actin, myosin, desmin, alpha-actinin, troponin and titin Mech Dev 116: 95–104CrossRefPubMedGoogle Scholar
  10. Dabiri GA, Turnacioglu KK, Sanger JM, Sanger JW, (1997) Myofibrillogenesis visualized in living embryonic cardiomyocytes Proc Natl Acad Sci USA 94:9493–9498CrossRefPubMedGoogle Scholar
  11. Dabiri GA, Turnacioglu KK, Ayoob JC, Sanger JM, Sanger JW, (1999a) Transfections of primary muscle cell cultures with plasmids coding for GFP linked to full-length and truncated muscle proteins Method Cell Biol 58:239–260Google Scholar
  12. Dabiri GA, Ayoob JP, Turnacioglu KK, Sanger JM, Sanger JW, (1999b) Use of Green Fluorescent Proteins linked to cytoskeletal proteins to analyze myofibrillogenesis in living cells Method Enzymol 302:171–186CrossRefGoogle Scholar
  13. Dlugosz AA, Antin PB, Nachmias VT, Holtzer H, (1984) The relationship between stress fiber-like structures and nascent myofibrils in cultured cardiac myocytes J Cell Biol 99: 2268–2278CrossRefPubMedGoogle Scholar
  14. Du A, Sanger JM, Linask KK, Sanger JW, (2003a) Myofibrillogenesis in the first cardiomyocytes formed from isolated quail precardiac mesoderm Dev Biol 57: 382–394CrossRefGoogle Scholar
  15. Du A., Sanger JM, Sanger JW, (2003b) Cardiac myofibrillogenesis follows similar pathways in ovo, in explants, and in tissue culture Mol Biol Cell 14: 423aGoogle Scholar
  16. Ehler E, Rothen BM, Haemmerle SP, Komiyama M, Perriard JC, (1999) Myofibrillogenesis in the developing chicken heart: assembly of Z-disk, M-line and the thick filaments J Cell Sci 112: 1529–1539PubMedGoogle Scholar
  17. Engel AG, Banker BQ, (2004) Ultrastructural changes in diseased muscle. In: Engel AG, Franzini-Armstrong C, (eds.) Myology. (3rd Edition), McGraw-Hill, New York, 749–887Google Scholar
  18. Ervasti JM, (2003) Costameres: the Achilles’ heel of Herculean muscle J Biol Chem 278: 13591–13594CrossRefPubMedGoogle Scholar
  19. Fallon JR, Nachmias VT, 1980. Localization of cytoplasmic and skeletal myosins in developing muscle cells by double-label immunofluorescence J Cell Biol 87:237–247CrossRefPubMedGoogle Scholar
  20. Faulkner G, Lanfranchi G, Valle G, (2001). Telethonin and other new proteins of the Z-disc of skeletal muscle IUBMB Life 51: 275–282PubMedCrossRefGoogle Scholar
  21. Feramisco JR, (1979) Microinjection of fluorescently labeled alpha-actinin into living fibroblasts Proc Natl Acad Sci USA 76: 3967–39671PubMedCrossRefGoogle Scholar
  22. Ferrari MB, Ribbeck K, Hagler DJ, Spitzer NC, (1998) A calcium cascade essential for myosin thick filament assembly in Xenopus myocytes J Cell Biol 141:1349–1356CrossRefPubMedGoogle Scholar
  23. Fischman DA, (1967) An electron microscope study of myofibril formation in embryonic chick skeletal muscle J Cell Biol 32: 557–575CrossRefPubMedGoogle Scholar
  24. Goldstein MA, Cartwright J, (1982) Microtubules in adult mammalian muscle. In: Dowben RM, Shay JW, (eds.) Cell and Muscle Motility Plenum Press New York, 85–92Google Scholar
  25. Golomb E, Ma X., Jana SS, Preston YA, Kawamoto S, Shoham NG, Goldin E, Conti MA, Sellers JR, Adelstein RS, (2004) Identification and characterization of nonmuscle myosin II-C, a new member of the myosin II family J Biol Chem 279: 2800–2808CrossRefPubMedGoogle Scholar
  26. Golson ML, Sanger JM, Sanger JW, (2004) Inhibitors arrest myofibrillogenesis in skeletal muscle cells at early stages of assembly Cell Motil Cytoskeleton 59:1–16CrossRefPubMedGoogle Scholar
  27. Gregorio CC, Antin PB, (2000) To the heart of myofibril assembly Trends Cell Biol 10: 355–362CrossRefPubMedGoogle Scholar
  28. Gundersen GG, Khawaja S, Bulinski JC, (1989) Generation of a stable, posttranslationally modified microtubule array is an early event in myogenic differentiation J Cell Biol 109: 2275–2288CrossRefPubMedGoogle Scholar
  29. Holtzer H, Hijikata T, Lin ZX, Zhang ZQ, Holtzer S, Protasi F, Franzini-Armstrong C, Sweeney HL, (1997) Independent assembly of 1.6 micron long bipolar MHC filaments and I-Z-I bodies Cell Struc Funct 22:83–93CrossRefGoogle Scholar
  30. Imanaka-Yoshida K, Danowski BA, Sanger JM, Sanger JW, (1996) Living adult rat cardiomyocytes in culture: evidence for dissociation of costameric distribution of vinculin from costameric distributions of attachments Cell Motil Cytoskeleton 33: 263–275CrossRefPubMedGoogle Scholar
  31. Kaneko H, Okamoto M, Goshima K, (1984) Structural change of myofibrils during mitosis of newt embryonic myocardial cells in culture Exp Cell Res 153: 483–498CrossRefPubMedGoogle Scholar
  32. Kelly DE, (1969) Myofibrillogenesis and Z-band differentiation Anat Rec 163: 403–426CrossRefPubMedGoogle Scholar
  33. Kelly AM, Chacko S, (1976) Myofibril organisation and mitosis in cultured cardiac muscle cells Dev Biol 48: 421–430CrossRefPubMedGoogle Scholar
  34. Knoll R, Hoshijima M, Hoffman HM, Person V, Lorenzen-Schmidt I, Bang ML, Hayashi T, Shiga N, Yasukawa H, Schaper W, McKenna W, Yokoyama M, Schork NJ, Omens JH, McCulloch AD, Kimura A, Gregorio CC, Poller W, Schaper J, Schultheiss HP, Chien KR, (2002) The MLP family of cytoskeletal Z disc proteins and dilated cardiomyopathy: a stress pathway model for heart failure progression Cold Spring Harb Symp Quant Biol 67: 399–408CrossRefPubMedGoogle Scholar
  35. Langanger G, Moeremans M, Daneels G, Sobieszek A, De Brabander M, De Mey J, (1986) The molecular organization of myosin in stress fibers of cultured cells J Cell Biol 102: 200–209CrossRefPubMedGoogle Scholar
  36. LoRusso SM, Rhee D, Sanger JM, Sanger JW, (1997) Premyofibrils in spreading adult cardiomyoctes in tissue culture: evidence for re-expression of the embryonic program in adult cells Cell Motil Cytoskeleton 37:183–198CrossRefPubMedGoogle Scholar
  37. Lu MH, DiLullo C, Schultheiss T, Holtzer S, Murray JM, Choi J, Fischman DA, Holtzer H, (1992) The vinculin/sarcomeric-alpha-actinin/alpha-actin nexus in cultured cardiac myocytes J Cell Biol 117: 1007–1022CrossRefPubMedGoogle Scholar
  38. Mangan ME, Olmsted JB, (1996) A muscle-specific variant of microtubule-associated protein 4 (MAP4) is required in myogenesis Development 122: 771–781PubMedGoogle Scholar
  39. Maruyama KM, Kuroda M, Nonomura Y, (1985) Association of chicken pectoralis muscle phosphorylase with the Z-line and the M-line of myofibrils: comparison with ‘amorphin’, the amorphous component of the Z-line Biochim Biophys Acta 829: 229–237PubMedGoogle Scholar
  40. McKenna NM, Meigs JB, Wang YL, (1985) Exchangeability of alpha-actinin in living cardiac fibroblasts and muscle cells J Cell Biol 101: 2223–2232CrossRefPubMedGoogle Scholar
  41. Mitchell PO, Pavlath GK, (2002) Multiple roles of calcineurin in skeletal muscle growth Clin Orthop 403S: S197–S202Google Scholar
  42. Mittal B, Sanger JM, Sanger JW, (1987) Binding and distribution of filamin in permeabilized and living non-muscle and muscle cells Cell Motil Cytoskeleton 8:345–359CrossRefPubMedGoogle Scholar
  43. Moncman CL, Wang K, (1996) Assembly of nebulin into the sarcomeres of avian skeletal muscle Cell Motil Cytoskeleton 34: 167–184CrossRefPubMedGoogle Scholar
  44. Peng HB, Wolosewick JJ, Cheng PC, (1981) The development of myofibrils in cultured muscle cells: a whole-mount and thin-section electron microscopic study Dev Biol 88: 121–136CrossRefPubMedGoogle Scholar
  45. Rhee D, Sanger JM, Sanger JW, 1994. The premyofibril: evidence for its role in myofibrillogenesis Cell Motil Cytoskeleton 28:1–24CrossRefPubMedGoogle Scholar
  46. Rudy DE, Yatskievych TA, Antin PB, Gregorio CC, (2001) Assembly of thick, and thin, titin filaments in chick precardiac explants Dev Dyn 221: 61–71CrossRefPubMedGoogle Scholar
  47. Saitoh O, Arai T, Obinata T, (1988) Distribution of microtubules and other cytoskeletal filaments during myotube elongation as revealed by fluorescence microscopy Cell Tissue Res 252: 263–273CrossRefPubMedGoogle Scholar
  48. Sanger JM, Sanger JW, (1980) Banding and polarity of actin filaments in interphase and cleaving cells J Cell Biol 86:568–575CrossRefPubMedGoogle Scholar
  49. Sanger JM, Sanger JW, (2000) Assembly of cytoskeletal proteins into cleavage furrows of tissue culture cells Microsc Res Techniq 49: 190–201CrossRefGoogle Scholar
  50. Sanger JW, Sanger JM, (2001a) Fishing out proteins that bind to titin J Cell Biol 154:21–24CrossRefGoogle Scholar
  51. Sanger JW, Sanger JM, (2001b) Green fluorescent proteins improve myofibril research Biophoton Int 8: 44–46Google Scholar
  52. Sanger JW, Sanger JM, (2002) Myofibrillogenesis in cardiac muscle cells. In: Dube D, (ed.) Myofibrillogenesis. Springer Verlag, New York, 3–20Google Scholar
  53. Sanger JW, Mittal B, Sanger JM, (1984) Formation of myofibrils in spreading chick cardiac myocytes Cell Motil 4:405–416CrossRefPubMedGoogle Scholar
  54. Sanger JM, Mittal B, Pochapin MB, Sanger JW, (1986a) Myofibrillogenesis in living cells microinjected with fluorescently labeled alpha-actinin J Cell Biol 102:2053–2066 CrossRefGoogle Scholar
  55. Sanger JM, Mittal B, Pochapin MB and Sanger JW (1986b) Observations of microfilament bundles in living cells microinjected with fluorescently labeled contractile proteins. J Cell Sci Suppl 5: 17–44Google Scholar
  56. Sanger JW, Ayoob JC, Chowrashi P, Zurawski. D, Sanger JM, (2000) Assembly of myofibrils in cardiac muscle cells Advan Exper Med Biol 481: 89–102Google Scholar
  57. Sanger JW, Chowrashi P, Shaner NC, Spalthoff S, Wang J, Freeman N, Sanger JM, (2002) Myofibrillogenesis in skeletal muscle cells Clin Ortho 403S: S153–S162CrossRefGoogle Scholar
  58. Sanger JW, Sanger JM, Franzini-Armstrong C, (2004) Assembly of the skeletal muscle cell. In: Engel AG, Franzini-Armstrong C, (eds.) Myology. (3rd Edition), McGraw-Hill New York, 45–65Google Scholar
  59. Schaub MC, Hefti MA, Harder BA, Eppenberger HM, (1997) Various hypertrophic stimuli induce distinct phenotypes in cardiomyocytes J Mol Med 75: 901–920CrossRefPubMedGoogle Scholar
  60. Siebrands CC, Sanger JM, Sanger JW, (2004) Myofibrillogenesis in skeletal muscle cells in the presence of taxol Cell Motil Cytoskeleton 58: 39–52CrossRefPubMedGoogle Scholar
  61. Toyama Y, Forry-Schaudies S, Hoffman B, Holtzer H, (1982) Effects of taxol and colcemid on myofibrillogenesis Proc Natl Acad Sci USA 79: 6556–6560PubMedCrossRefGoogle Scholar
  62. Tskhovrebova L, Trinick J, (2004) Titin: properties and family relationships Nat Rev Mol Cell Biol 4: 679–689CrossRefGoogle Scholar
  63. Tullio AN, Accili D, Ferrans VJ, Yu ZX, Takeda K, Grinberg A, Westphal H, Preston YA, Adelstein RS, (1997) Nonmuscle myosin II-B is required for normal development of the mouse heart Proc Natl Acad Sci USA 94: 12407–12412CrossRefPubMedGoogle Scholar
  64. Turnacioglu KK, Mittal B, Sanger JM, Sanger JW, (1996) Partial characterization of zeugmatin indicates that is part of the Z-band region of titin Cell Motil Cytoskeleton 34:108–121CrossRefPubMedGoogle Scholar
  65. Wang J, Shaner NC, Mittal B, Zhou Q, Chen J, Sanger JM, Sanger JW, (2005a) Dynamics of Z-band based proteins in developing skeletal muscle cells Cell Motil Cytoskeleton 61: 34–48CrossRefGoogle Scholar
  66. Wang J, Sanger JM and Sanger JW, (2005b) Differential effects of latrunculin-A on myofibrils in cultures of skeletal muscle cells: insights into mechanisms of myofibrillogenesis. Cell Motil Cytoskeleton 62: 35–47CrossRefGoogle Scholar
  67. Warren RH, (1968) The effect of colchicine on myogenesis in vivo in Rana pipiens and Rhodnius prolixus (Hemiptera) J Cell Biol 63: 550–566CrossRefGoogle Scholar
  68. Warren RH, (1974) Microtubular organization in elongating myogenic cells J Cell Biol 39: 544–555CrossRefGoogle Scholar
  69. Zhukarev V, Sanger JW, Sanger JM, Goldman Y, Shuman H, (1997) Steady state fluorescence polarization analysis of rhodamine phalloidin binding to muscle Cell Motil Cytoskeleton 37: 363–377CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Joseph W. Sanger
    • 1
    Email author
  • Songman Kang
    • 1
  • Cornelia C. Siebrands
    • 1
  • Nancy Freeman
    • 1
  • Aiping Du
    • 1
  • Jushuo Wang
    • 1
  • Andrea L. Stout
    • 1
  • Jean M. Sanger
    • 1
  1. 1.Department of Cell and Developmental BiologyUniversity of Pennsylvania School of MedicinePhiladelphiaUSA

Personalised recommendations