Skip to main content
SpringerLink
Log in

Titin and Nebulin: Giant Multitasking Protein Rulers in Muscle

  • Conference paper
The Cytoskeleton

  • 50 Accesses

Abstract

When a striated muscle cell is stimulated, e.g. by nerve impulses, it is activated from the resting state. It develops contractile force, shortens, and then relengthens to its original dimension when stimulation ceases. The resting muscle, in the absence of any stimulation, is remarkably elastic when stretched and released. More than a century of muscle research has focused on the understanding of the structure and molecular processes which underlie active contraction. The widely accepted sliding filament model states that muscle develops active force by the cyclic attachment and detachment of myosin crossbridges to actin filaments and that muscle shortens when actin filaments are pulled to slide pass thick filaments, without changing the length of either filament (Huxley 1990). Despite major advances in the understanding of the molecular basis of active contraction, surprisingly little is known of how contracted muscle restores its length and how resting muscle responds to stretch and compression. It is also unclear how muscle cells manage to control the uniform and precise length of thick and thin filaments in the sarcomere. Recent studies of sarcomere-associated cytoskeletal lattices begin to shed light on both questions (reviewed by Wang 1985; Maruyama 1986, 1994; Price 1991; Trinick 1992).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Benian GM, Kiff JE, Neckelmann N, Moerman DG, Waterston RH (1989) Sequence of an unusually large protein implicated in regulation of myosin activity in C. elegans. Nature 342: 45–50

    Article  PubMed  CAS  Google Scholar 

  • Caldwell JE, Heiss SG, Mermall V, Cooper JA (1989) Effects of CapZ, an actin capping protein of muscle, on the polymerization of actin. Biochemistry 28: 8506–8514

    Article  PubMed  CAS  Google Scholar 

  • Chen M-JG, Shih C-L, Wang K (1993) Nebulin as an actin zipper. J Biol Chem 268: 20327–20334

    PubMed  CAS  Google Scholar 

  • Colley NJ, Tokuyasu KT, Singer SJ (1990) The early expression of myofibrillar proteins in rounded postmitotic myoblasts of embryonic skeletal muscle. J Cell Sci 95: 11–22

    PubMed  CAS  Google Scholar 

  • Eilertsen KJ, Keller TCS (1992) Identification and characterization of two huge protein com¬ponents of the brush border cytoskeleton: evidence for a cellular isoform of titin. J Cell Biol 119: 549–557

    Article  PubMed  CAS  Google Scholar 

  • Epstein HF, Fischman DA (1991) The molecular basis of protein assembly in muscle develop¬ment. Science 251: 1039–1044

    Article  PubMed  CAS  Google Scholar 

  • Fulton AB, Isaacs WB (1991) Titin, a huge, elastic sarcomeric protein with a probable role in morphogenesis. Bio Essays 13: 157–161

    CAS  Google Scholar 

  • Furst DO, Osborn M, Nave R, Weber K (1988) The organization of titin filaments in the half sarcomere revealed by monoclonal antibodies in immunoelectron microscopy: a map of ten nonrepetitive epitopes starting at the Z line extends close to the M line. J Cell Biol 106: 1563–1572

    Article  PubMed  CAS  Google Scholar 

  • Fiirst DO, Osbom M, Weber K (1989) Myogenesis in the mouse embryo: differential onset of expression of myogenic proteins and the involvement of titin in myofibril assembly. J Cell Biol 109: 517–527

    Article  Google Scholar 

  • Granzier HLM, Wang K (1993a) Interplay between passive tension and strong and weak binding cross-bridges in insect indirect flight muscle. J Gen Physiol 101: 235–270

    Article  PubMed  CAS  Google Scholar 

  • Granzier HLM, Wang K (1993b) Passive tension and stiffness of vertebrate skeletal and insect flight muscles: the contribution of weak cross-bridges and elastic filaments. Biophys J 65: 2141–2159

    Article  PubMed  CAS  Google Scholar 

  • Handel SE, Greaser ML, Schultz E, Wang S-M, Bulinski JC, Lin JJ, Lessard J (1991) Chicken cardiac myofibrillogenesis: studies with antibodies specific for titin and the muscle and nonmuscle isoforms of actin and tropomyosin. Cell Tissue Res 263: 419–430

    Article  PubMed  CAS  Google Scholar 

  • Handel SE, Wang SM, Greaser ML, Schultz E, Bulinski JC, Lessard JL (1989) Skeletal muscle myofibrillogenesis as revealed with a monoclonal antibody to titin in combination with detection of the a- and y-isoforms of actin. Dev Biol 132: 35–44

    Article  PubMed  CAS  Google Scholar 

  • Higuchi H (1992) Changes in contractile properties with selective digestion of connectin (titin) in skinned fibers of frog skeletal muscle. J Biochem 111: 291–295

    PubMed  CAS  Google Scholar 

  • Higuchi H, Suzuki K, Yoshioka T, Marayama K, Umazume Y (1992) Localization and elasticity of connectin (titin) filaments in skinned frog muscle fibres subjected to partial depolymerization of thick filaments. J Mus Res Cell Motil 13: 285–294

    Article  CAS  Google Scholar 

  • Hill CS, Duran S, Lin Z, Weber K, Holtzer H (1986) Titin and myosin, but not desmin, are linked during myofibrillogenesis in postmitotic mononucleated myoblasts. J Cell Biol 103: 2185–2196

    Article  PubMed  CAS  Google Scholar 

  • Horowits R, Podolsky RJ (1987) The positional stability of thick filaments in activated skeletal muscle depends on sarcomere length: evidence for the role of titin filaments. J Cell Biol 105: 2217–2223

    Article  PubMed  CAS  Google Scholar 

  • Horowits R, Kempner ES, Bisher ME, Podolsky RJ (1986) A physiological role for titin and nebulin in skeletal muscle. Nature 323: 160–164

    Article  PubMed  CAS  Google Scholar 

  • Huxley HE (1990) Sliding filaments and molecular motile systems. J Biol Chem 265: 8347–8350

    PubMed  CAS  Google Scholar 

  • Isaacs WB, Kim IS, Struve A, Fulton A (1992) Biosynthesis of titin and myosin heavy chain in developing skeletal muscle. Pro Natl Acad Sci USA 89: 7496–7500

    Article  CAS  Google Scholar 

  • Itoh Y, Suzuki T, Kimura S, Ohashi K, Higuchi H, Sawada H, Shimizu T, Shibata M, Maruyama K (1988) Extensible and less-extensible domains of connectin filaments in stretched vertebrate skeletal muscle sarcomeres as detected by immunofluorescence and immunoelectron microscopy using monoclonal antibodies. J Biochem 104: 504–508

    PubMed  CAS  Google Scholar 

  • Jin J-P, Wang K (1991) Cloning, expression and protein interaction of human nebulin fragments composed of varying numbers of sequence modules. J Biol Chem 266: 21215–21223

    PubMed  CAS  Google Scholar 

  • Komiyama M, Zhou Z-H, Maruyama K, Shimada Y (1992) Spatial relationship of nebulin relative to other myofibrillar proteins during myogenesis in embryonic chick skeletal muscle cells in vitro. J Mus Res Cell Motil 13: 48–54

    Article  CAS  Google Scholar 

  • Koretz JF, Irving TC, Wang K (1993) Filamentous aggregates of native titin and binding of C protein and AMP-deaminase. Arch Biochem Biophys 304: 305–309

    Article  PubMed  CAS  Google Scholar 

  • Kruger M, Wright J, Wang K (1991) Nebulin as a length regulator of thin filaments of vertebrate skeletal muscles: correlation of thin filament length, nebulin size and epitope profile. J Cell Biol 115: 97–107

    Article  PubMed  CAS  Google Scholar 

  • Labeit S, Gautel M, Lakey A, Trinick J (1992) Towards a molecular understanding of titin. EMBO J 11: 1711–1716

    PubMed  CAS  Google Scholar 

  • Labeit S, Gibson T, Lakey A, Leonard K, Zeviani M, Knight P, Wardale J, Trinick J (1991) Evidence that nebulin is a protein-ruler in muscle thin filaments. FEBS Lett 282: 313–316

    Article  PubMed  CAS  Google Scholar 

  • Locker RH, Wild DJC (1986) A comparative study of high molecular weight proteins in various types of muscles across the animal kingdom. J Biochem 99: 1473–1484

    PubMed  CAS  Google Scholar 

  • Maroto M, Vinos J, Marco R, Cervera M (1992) Autophosphorylating protein kinase activity intitin-like arthropod projectin. J Mol Biol 224: 287–291

    Article  PubMed  CAS  Google Scholar 

  • Maruyama K (1986) Connectin, an elastic filamentous protein of striated muscle. In Rev Cytol 104: 81–114

    Google Scholar 

  • Maruyama K (1994) Connectin, an elastic protein of striated muscle. Biophys Chem 50: 73–85

    Article  PubMed  CAS  Google Scholar 

  • Maruyama K, Matsubara S, Natori R, Nonomura Y, Kimura S, Ohashi K, Murakami F, Handa F, Eguchi G (1977) Connectin, an elastic protein of muscle. J Biochem 82: 317–337

    PubMed  CAS  Google Scholar 

  • Maruyama K, Kimura S, Yoshidomi H, Sawada H, Kikuchi M (1984) Molecular size and shape of 3-connectin, an elastic protein of striated muscle. J Biochem 95: 1423–1433

    PubMed  CAS  Google Scholar 

  • Maruyama T, Nakauchi Y, Kimura S, Maruyama K (1989) Binding of connectin to myosin filaments. J Biochem 105: 323–326

    PubMed  Google Scholar 

  • Matsumura F, Yamashiro S (1993) Caldesmon. Curr Opinion Cell Biol 5: 70–76

    Article  CAS  Google Scholar 

  • Musacchio A, Gibson T, Lehto V-P, Saraste M (1992) SH3 - an abundant protein domain in search of a function. FEBS Lett 307: 55–61

    Article  PubMed  CAS  Google Scholar 

  • Nave R, Ftirst DO, Weber K (1989) Visualization of the polarity of isolated titin molecules: a singular globular head on a long rod as the M band anchoring domain? J Cell Biol 109: 2177–2187

    Article  PubMed  CAS  Google Scholar 

  • Nave R, Fiirst DO, Weber K (1990) Interaction of a-actinin and nebulin in vitro: support for the existence of a fourth filament system in skeletal muscle. FEBS Lett 269: 163–166

    Article  PubMed  CAS  Google Scholar 

  • Nave R, Fiirst D, Vinkemeier U, Weber K (1991) Purification and physical properties of nematode mini-titins and their relation to twitchin. J Cell Sci 98: 491–496

    PubMed  CAS  Google Scholar 

  • Pfuhl M, Winder SJ, Pastore A (1994) Nebulin, a helical actin binding protein. EMBO J 13: 1782–1789

    PubMed  CAS  Google Scholar 

  • Pierobon-Bormioli S, Betto R, Salviati G (1989) The organization of titin (connectin) and nebulin in the sarcomeres: an immunocytolocalization study. J Mus Cell Mot 10: 446–456

    Article  CAS  Google Scholar 

  • Politou AS, Gauel M, Pfuhl M, Labeit S, Pastore A (1994) Immunoglobulin-type domains of titin: same fold, different stability. Biochemistry 33: 4730–4737

    Article  PubMed  CAS  Google Scholar 

  • Price MG (1991) Striated muscle endosarcomeric and exosarcomeric lattices. Adv Struct Biol 1: 175–208

    Google Scholar 

  • Pudles J, Mondjou M, Hisanaga S-I, Maruyama K, Sakai H (1990) Isolation, characterization and immunochemical properties of a giant protein from sea urchin egg cytomatrix. Exp Cell Res 189: 253–260

    Article  PubMed  CAS  Google Scholar 

  • Roberts TM (1987) Fine (2-5-nm) filaments: new types of cytoskeletal structures. Robinson RF, Winegrad S (1979) The measurement and dynamic implications of thin filament lengths in heart muscle. J Physiol 286: 607–619

    Google Scholar 

  • Root D, Wang K (1994) Calmodulin sensitive interaction of human nebulin fragments with actin and myosin. Biochemistry 33: 12581–1259

    Article  PubMed  CAS  Google Scholar 

  • Saide JD (1981) Identification of a connecting filament protein in insect fibrillar flight muscle.

    Google Scholar 

  • J Mol Biol 153:661-679 Schultheiss T, Lin Z, Lu MH, Murray J, Fischman DA, Weber K, Masaki T, Imamura M, Holtzer H (1990) Differential distribution of subsets of myofibrillar protein in cardiac non- striated and striated myofibrils. J Cell Biol 110:1159-1172 Somerville L, Wang K (1988) Sarcomere matrix of striated muscle: in vivo phosphorylation of titin and nebulin in mouse diaphragm muscle. Arch Biochem Biophys 262:118–129

    Google Scholar 

  • Soteriou A, Clarke A, Martin S, Trinick J (1993a) Titin folding energy and elasticity. Proc R Soc Lond B 254: 83–86

    Article  CAS  Google Scholar 

  • Soteriou A, Gamage M, Trinick J (1993b) A survey of interactions made by the giant protein titin. J Cell Sci 104: 119–123

    PubMed  CAS  Google Scholar 

  • Stedman H, Browning K, Oliver N, Oronzi-Scott M, Fischbeck K, Sarkar S, Sylvester J, Schmickel R, Wang K (1988) Nebulin cDNAs detect a 25-kilobase transcript in skeletal muscle and localize to human chromosome 2. Genomics 2: 1–7

    Article  PubMed  CAS  Google Scholar 

  • Stromer MH (1992) Immunocytochemical localization of proteins in striated muscle. Int Rev Cytol 142: 61–144

    Article  PubMed  CAS  Google Scholar 

  • Takano-Ohmuro H, Nakauchi Y, Kimura S, Maruyama K (1992) Autophosphorylation of connectin (titin 2) in vitro. Biochem Biophys Res Commun 183: 31–35

    Article  PubMed  CAS  Google Scholar 

  • Tatsumi R, Hattori A, Takahashi K (1992) Purification and characterization of nebulin sub-fragments produced by 0.1 mM CaCl2. J Biochem 112: 780–785

    PubMed  CAS  Google Scholar 

  • Terai M, Komiyana M, Shimada Y (1989) Myofibril assembly is linked with vinculin, actinin and cell substrate contacts in embryonic cardiac myocytes in vitro. Cell Mot Cytoskel 12: 185–191

    Article  CAS  Google Scholar 

  • Tokuyasu KT, Maher PA (1987) Immunocytochemical studies of cardiac myofibrillogenesis in early chick embryos. II. Generation of a-actinin dots within titin spots at the time of the first myofibril formation. J Cell Biol 105: 2795–2801

    Google Scholar 

  • Trinick J (1992) Understanding the functions of titin and nebulin. FEBS Lett 307: 44–48

    Article  PubMed  CAS  Google Scholar 

  • Trinick J, Knight P, Whiting A (1984) Purification and properties of native titin. J Mol Biol 180: 331–356

    Article  PubMed  CAS  Google Scholar 

  • Uchida K, Harada I, Nakauchi Y, Maruyama K (1991) Structural properties of connectin studied by ultraviolet resonance Raman spectroscopy and infrared dichroism. FEBS Lett 296: 35–38

    Article  Google Scholar 

  • van der Ven PEM, Schaart G, Croes HJE, Jap PHK, Ginsel LA (1993) Titin aggregates associated with intermediate filaments align along stress fiber-like structures during human skeletal muscle cell differentiation. J Cell Sci 106: 749–759

    PubMed  Google Scholar 

  • Vibert P, Edelstein SM, Castellani L, Elliott BWJ (1993) Mini-titins in striated and smooth molluscan muscles: structure, location and immunological crossreactivity. J Mus Res Cell Motil 14: 598–607

    Article  CAS  Google Scholar 

  • Vinkemeier U, Obermann W, Weber K, Flirst DO (1993) The globular head domain of titin extends into the center of the sarcomeric M band. J Cell Sci 106: 319–330

    PubMed  CAS  Google Scholar 

  • Wang K (1985) Sarcomere-associated cytoskeletal lattices in striated muscle, pp. 315-369. In.: Shay JW (ed) Cell muscle motility, vol 6. Plenum, New York

    Google Scholar 

  • Wang K, Ramirez-Mitchel R (1983) Ultrastructural morphology and epitope distribution of titin - a giant sarcomere-associated cytoskeletal protein. J Cell Biol 97: 986a

    Google Scholar 

  • Wang K, Wright J (1988) Architecture of the sarcomere matrix of skeletal muscle: immuno- electron microscopic evidence that suggests a set of parallel inextensible nebulin filaments anchored at the Z line. J Cell Biol 107: 2199 - 2212

    Article  PubMed  CAS  Google Scholar 

  • Wang K, McClure J, Tu A (1979) Titin: major myofibrillar components of striated muscle. Proc Natl Acad Sci USA 76: 3698–3702

    Article  PubMed  CAS  Google Scholar 

  • Wang K, Ramirez-Mitchel R, Palter D (1984) Titin is an extraordinarily long, flexible, and slender myofibrillar protein. Proc Natl Acad Sci USA 81: 3685–3689

    Article  PubMed  CAS  Google Scholar 

  • Wang K, Knipfer M, Huang QQ, Hsu L, van Heerden A, Browning K, Quian X, Stedman H (1990) Structural motifs of nebulin as predicted by sequences of human nebulin cDNA. J Cell Biol 111: 428a

    Google Scholar 

  • Wang K, McCarter R, Wright J, Beverly J, Ramirez-Mitchell R (1993) Viscoelasticity of the sarcomere matrix of skeletal muscles: the titin-myosin composite filament is a dual-stage molecular spring. Biphys J 64: 1161–1177

    Article  CAS  Google Scholar 

  • Wright J, Huang Q-Q, Wang K (1993) Nebulin is a full-length template of actin filaments in the skeletal muscle sarcomere: an immunoelectron microscopic study of its orientation and span with site-specific monoclonal antibodies. J Mus Res Cell Motil 14: 476–483

    Article  CAS  Google Scholar 

  • Zeviani M, Darras BT, Rizzuto R, Salviati G, Betto R, Bonilla E, Miranda AF, Du J, Samitt C, Dickson G, Walsh FS, Dimauro S, Francke U, Schon EA (1988) Cloning and expression of human nebulin cDNAs and assignment of the gene to chromosome 2q31-q32. Genomics 2: 249–256

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry and Biochemistry, Biochemical Institute and Cell Research Institute, University of Texas at Austin, Austin, Texas, 78712, USA

    K. Wang

Authors
  1. K. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Zoologisches Institut Abteilung Zellbiologie, Technische Universität Braunschweig, Spielmannstr.7, D-38092, Braunschweig, Germany

    B. M. Jockusch

  2. AG für strukturelle Molekularbiologie, Max-Planck-Gesellschaft, Notkestr. 85, D-22607, Hamburg, Germany

    E. Mandelkow

  3. Max-Plank-Institut für Biophysikalische Chemie, Am Faßberg, D-37018, Göttingen, Germany

    K. Weber

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Wang, K. (1995). Titin and Nebulin: Giant Multitasking Protein Rulers in Muscle. In: Jockusch, B.M., Mandelkow, E., Weber, K. (eds) The Cytoskeleton. Colloquium der Gesellschaft für Biologische Chemie 14.–16. April 1994 in Mosbach/Baden, vol 45. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79482-7_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-79482-7_11

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-79484-1

  • Online ISBN: 978-3-642-79482-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation