The titin cDNA sequence and partial genomic sequences: Insights into the molecular genetics, cell biology and physiology of the titin filament system

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References

  • Aarli JA, Stefansson K, Marton LSG & Wollmann RL (1990) Patients with myasthenia gravis and thymoma have in their sera IgG autoantibodies against titin. Clin Exp Immunol 82:284–288

    PubMed  CAS  Google Scholar 

  • Beggs AH, Byers TJ, Knoll JHM, Boyce FM, Bruns GAP & Kunkel LM (1992) Cloning and characterization of two human skeletal muscle alpha-actinin genes located on chromosomes 1 and 11. J Biol Chem 267:9281–9288

    PubMed  CAS  Google Scholar 

  • Bennett PM & Gautel M (1996) Titin domain patterns correlate with the axial disposition of myosin at the end of the thick filament. J Mol Biol 255:604–616

    Article  Google Scholar 

  • Bonne G, Carrier L, Bercovici J, Cruaud C, Richard P, Hainque B, Gautel M, Labeit S, James M, Weissenbach J, Vosberg HP, Fiszman M, Komajda M & Schwartz K (1995) Cardiac myosin binding protein-C gene splice acceptor site mutation is associated with familial hypertrophic cardiomyopathy. Nature Genetics 11:438–440

    Article  PubMed  CAS  Google Scholar 

  • Carrier L, Bonne G, Bährend E, Yu B, Richard P, Niel F, Hainque B, Cruaud C, Gary F, Labeit S, Bouhour J-B, Dubourg O, Desnos M, Hagège AA, Trent RJ, Komajda M, Fiszman M & Schwartz K (1997) Organization and sequence of human cardiac myosin binding protein C gene (MYBPC3) and identification of mutations predicted to produce truncated proteins in familial hypertrophic cardiomyopathy. Circ Res 80:427–434

    PubMed  CAS  Google Scholar 

  • Cox DR (1995) Map** with radiation hybrids. Genome Digest 4:14–15

    Google Scholar 

  • Craig R & Offer G (1976) The location of C-protein in rabbit skeletal muscle. Proc R Soc Ser B 192:325–332

    Google Scholar 

  • Craig R (1977) Structure of A-segments from frog and rabbit skeletal muscle. J Mol Biol 109:69–81

    Article  PubMed  CAS  Google Scholar 

  • Fields S & Song O (1989) A novel genetic system to detect protein-protein interactions. Nature 340:245–246

    Article  PubMed  CAS  Google Scholar 

  • Freiburg A & Gautel M (1996) A molecular map of the interactions between titin and myosin-binding protein C. Implications for sarcomeric assembly in familial hypertrophic cardiomyopathy. Eur J Biochem 235:317–323

    Article  PubMed  CAS  Google Scholar 

  • Fürst 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  Google Scholar 

  • Fulton AB & Isaacs WB (1991) Titin, a huge, elastic sarcomeric protein with a probable role in morphogenesis. Bioessays 13:157–61

    Article  PubMed  CAS  Google Scholar 

  • Funatsu T, Higuchi H & Ishiwata S (1990) Elastic filaments in skeletal muscle revealed by selective removal of thin filaments with plasma gelsolin. J Cell Biol 110:53–62

    Article  PubMed  CAS  Google Scholar 

  • Gautel M & Goulding D (1996) A molecular map of titin/connectin elasticity reveals two different mechanisms acting in series. FEBS Lett 385:11–4

    Article  PubMed  CAS  Google Scholar 

  • Gautel M, Leonard K & Labeit S (1993a) Phosphorylation of KSP-motifs in the Cterminal region of titin in differentiating myoblasts. EMBO J 12:3827–3834

    PubMed  CAS  Google Scholar 

  • Gautel M, Lakey A, Barlow DP, Holmes Z, Scales S, Leonard K, Labeit S, Mygland A, Gilhus N E & Aarli J (1993b) Titin antibodies in myasthenia gravis: Identification of a major auto-immunogenic region of titin. Neurology 43:1581–1585

    PubMed  CAS  Google Scholar 

  • Gautel M, Zuffardi O, Freiburg A & Labeit S (1995) A cooperative phosphorylation switch in human cardiac myosin-binding protein C specific for the cardiac isoform: A modulator of cardiac contraction? EMBO J 14:1952–1960

    PubMed  CAS  Google Scholar 

  • Gautel M, Goulding D, Bullard B, Weber K & Fürst DO (1996) The central Z-disk region of titin is assembled from a novel repeat in variable copy numbers. J Cell Sci 109:2747–2754

    PubMed  CAS  Google Scholar 

  • Goldstein MA, Michael LH, Schroeter JP & Sass RL (1986) The Z-band lattice in skeletal muscle before, during and after tetanic contraction. J Muscle Res Cell Motil 7:527–536

    Article  PubMed  CAS  Google Scholar 

  • Goldstein MA, Michael LH, Schroeter JP & Sass RL (1989) Two structural states of Zbands in cardiac muscle. Am J Physiol (Heart Circ Physiol) 256:H552–H559

    CAS  Google Scholar 

  • Granzier HL & Irving TC (1995) Passive tension in cardiac muscle: contribution of collagen, titin, microtubules and intermediate filaments. Biophys J 68:1027–1044

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Horowits R (1992) Passive force generation and titin isoforms in mammalian skeletal muscle. Biophys J 61:392–398

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Improta S, Politou AS & Pastore A (1996) Immunoglobulin-like modules from titin I-band: extensible components of muscle elasticity. Structure 4:323–337

    Article  PubMed  CAS  Google Scholar 

  • Kinbara K, Sorimachi H, Ishiura S & Suzuki K (1997) Muscle-specific calpain, p94, interacts with the extreme C-terminal region of connectin, a unique region flanked by two immunoglobulin C2 motifs. Arch Biochem Biophys 342:99–107

    Article  PubMed  CAS  Google Scholar 

  • Kolmerer B, Olivieri N, Herrmann BG & Labeit S (1996a) A systematic search of the data bases for sequences homologous to titin/connectin. Advances in Biophysics 33:3–11

    Article  PubMed  CAS  Google Scholar 

  • Kolmerer B, Olivieri N, Herrmann BG & Labeit S (1996b) Genomic organization of the M-line titin and its tissue-specific expression in two distinct isoforms. J Mol Biol 256:556–563

    Article  PubMed  CAS  Google Scholar 

  • Labeit S, Barlow DP, Gautel M, Gibson T, Holt J, Hsieh CL, Francke U, Leonard K, Wardale J, Whiting A & Trinick J (1990) A regular pattern of two types of 100residue motif in the sequence of titin. Nature 345:273–276

    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 & Kolmerer B (1995) Titins, giant proteins in charge of muscle ultrastructure and elasticity. Science 270:293–296

    Article  PubMed  CAS  Google Scholar 

  • Labeit S, Kolmerer B & Linke WA (1997) The giant protein titin: Emerging roles in physiology and pathophysiology. Circ Res 80:290–294

    PubMed  CAS  Google Scholar 

  • Laing NG, Wilton SD, Akkari PA, Boundy K, Kneebone C, Blumbergs P, White S, Watkins H, Love DR & Haan E (1995) A mutation in the a-tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy. Nature Genet 9:75–79

    Article  PubMed  CAS  Google Scholar 

  • Linke WA, Bartoo, ML & Pollack GH (1993) Spontaneous sarcomeric oscillations at intermediate activation levels in single isolated cardiac myofibrils. Circ Res 73:724–734

    PubMed  CAS  Google Scholar 

  • Linke WA, Ivemeyer M, Olivieri N, Kolmerer B, Rüegg JC & Labeit S (1996) Towards a molecular understanding of the elasticity of titin. J Mol Biol 261:62–71

    Article  PubMed  CAS  Google Scholar 

  • Linke WA, Ivemeyer M, Labeit S, Hinssen H, Rüegg JC & Gautel M (1997) Actin-titin interaction in cardiac myofibrils: probing a physiological role. Biophys J 73:905–919

    PubMed  CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Maruyama K, Sawada H, Kimura S, Ohashi K, Higuchi H & Umazume Y (1984) Connectin filaments in stretched skinned fibers of frog skeletal muscle. J Cell Biol 99:1391–1397

    Article  PubMed  CAS  Google Scholar 

  • Maruyama K, Yoshioka T, Higuchi H, Ohashi K, Kimura S & Natori R (1985) Connectin filaments link thick filaments and Z lines in frog skeletal muscle as revealed by immunoelectron miscroscopy. J Cell Biol 101:2167–2172

    Article  PubMed  CAS  Google Scholar 

  • Müller-Seitz M, Kaupmann K, Labeit S & Jockusch H (1993) Chromosomal localization of the mouse titin gene and its relation to “muscular dystrophy with myositis” and nebulin genes on chromosome 2. Genomics 18:559–561

    Article  PubMed  Google Scholar 

  • Obermann WMJ, Gautel, M, Steiner, F, vanderVeen, PFM, Weber, K & Fürst DO (1996) The structure of the sarcomeric M band: localization of defined domains of myomesin, M protein, and the 250 kD carboxy terminal region of titin by immunoelectron microscopy. J Cell Biol 134:1441–1453

    Article  PubMed  CAS  Google Scholar 

  • Ohtsuka H, Yajima H, Maruyama K & Kimura S (1997a) Binding of the N-terminal 63 kDa portion of connectin/titin to alpha-actinin as revealed by the yeast twohybrid system. FEBS Lett 401:65–67

    Article  PubMed  CAS  Google Scholar 

  • Ohtsuka H, Yajima H, Maruyama K & Kimura S (1997b) The N-terminal Z repeat 5 of connectin/titin binds to the C-terminal region of alpha-actinin. Biochem Biophys Res Commun. 235:1–3

    Article  PubMed  CAS  Google Scholar 

  • Pelin K, Ridanpää M, Donner K, Wilton, S, Krishnarajah J, Laing N, Kolmerer B, Millevoi S, Labeit S, de la Chapelle A & Wallgren-Pettersson C (1997) Refined localization of the genes for nebulin and titin on chromosome 2q allows the assignment of nebulin as a candidate gene for autosomal recessive nemaline myopathy. Eur J Hum Genet 5:229–234

    PubMed  CAS  Google Scholar 

  • Pfuhl M & Pastore A (1995) Tertiary structure of an immunoglobulin-like domain from the giant muscle protein titin: a new member of the I set. Structure 3:391–401

    Article  PubMed  CAS  Google Scholar 

  • Politou A, Thomas DJ & Pastore A (1995) The folding and stability of titin immunoglobulin-like modules, with implications for the mechanism of elasticity. Biophys J69:2601–2610

    PubMed  CAS  Google Scholar 

  • Richard I, Broux O, Allamand V, Fougerousse F, Chiannilkulchai N, Bourg N, Brenguier L, Devaud C, Pasturaud P, Roudaut C, Hillaire D, Passos-Bueno MR, Zatz M, Tischfield JA, Fardeau M, Jackson CE, Cohen D & Beckmann JS (1995) Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy 2A. Cell 81: 27–40

    Article  PubMed  CAS  Google Scholar 

  • Rossi E, Faiella A, Zeviani M, Labeit S, Floridia G, Brunelli S, Cammarata M, Boncinelli E & Zuffardi O (1994) Order of six loci at 2q24-q31 and orientation of the HOXD locus. Genomics 24:34–40

    Article  PubMed  CAS  Google Scholar 

  • Rottbauer W, Gautel M, Zehelein J, Labeit S, Franz WM, Fischer C, Vollrath B, Mall G, Dietz R, Kübler W & Katus H (1997) A novel splice donor site mutation in the cardiac myosin binding protein-C gene in familial hypertrophic cardiomyopathy: Characterization of cardiac transcript and protein. J Clin Invest 100:475–482

    Article  PubMed  CAS  Google Scholar 

  • Saiki RK, Scharf SJ, Faloona F, Mullis GT & Erlich HA (1985) Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230:1350–1354

    Article  PubMed  CAS  Google Scholar 

  • Salviati G, Betto R, Ceoldo S & Pierobon-Bormioli S (1990) Morphological and functional characterization of the endosarcomeric elastic filament. Am J Physiol 259:C144–C149

    PubMed  CAS  Google Scholar 

  • Schroeter JP, Bretaudiere JP, Sass RL & Goldstein MA (1996) Three-dimensional structure of the Z band in a normal mammalian skeletal muscle. J Cell Biol 133:571–583

    Article  PubMed  CAS  Google Scholar 

  • Schultheiss T, Lin, Z, Lu M-H, Murray J, Fischman DA, Weber K, Masaki M, Imamura M & Holtzer H (1992a) Differential distribution of subsets of myofibrillar proteins in cardiac nonstriated and striated myofibrils. J Cell Biol 110:1159–1172

    Article  Google Scholar 

  • Schultheiss T, Choi J, Lin ZX, DiLullo C, Fischman DA & Holtzer H (1992b) A sarcomeric alpha-actinin truncated at the carboxyterminal end induces the breakdown of stress fibers in PtK2 cells and the formation of nemaline-like bodies and breakdown of myofibrils in myotubes. Proc Natl Acad Sci USA 89:9282–9286.

    Article  PubMed  CAS  Google Scholar 

  • Schwartz K, Carrier L, Guicheney P & Komajda M (1995) The molecular basis of cardiomyopathies. Circulation 91:532–540

    PubMed  CAS  Google Scholar 

  • Sebestyan MG, Wolff JA & Greaser ML (1995) Characterization of a 5.4 kb cDNA fragment from the Z-line region of rabbit cardiac titin reveals phosphorylation sites for proline-directed kinases. J Cell Sci 108:3029–3037

    Google Scholar 

  • Sjöström M & Squire JM (1977) Fine structure of the A-band in cryosections. J Mol Biol 109:49–68

    Article  PubMed  Google Scholar 

  • Sorimachi H, Kinbara K, Kimura S, Takahashi M, Ishiura S, Sasagawa N, Sorimachi N, Shimada H, Tagawa K, Maruyama K & Suzuki K (1995) Muscle-specific calpain, p94, responsible for limb girdle muscular dystrophy type 2A, associates with connectin through IS2, a p94-specific sequence. J Biol Chem 270:31158–31162

    Article  PubMed  CAS  Google Scholar 

  • Sorimachi H, Freiburg A, Kolmerer B, Ishiura S, Stier G, Gregorio CC, Labeit D, Linke WA, Suzuki K & Labeit S (1997) Tissue-specific expression and alphaactinin binding properties of the Z disc titin. Implications for the nature of vertebrate Z discs. J Mol Biol 270:688–695

    Article  PubMed  CAS  Google Scholar 

  • Squire JM (1981) The structural basis of muscular contraction. New York, Plenum Press

    Google Scholar 

  • Squire JM (1997) Architecture and function in the muscle sarcomere. Curr Opinion Struct Biol 7: 247–257

    Article  CAS  Google Scholar 

  • Thierfelder L, Watkins H, McRae C, Lamas R, McKenna W, Vosberg HP, Seidman JG & Seidman CE (1994) Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. Cell 77:701–712

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Trinick J (1994) Titin and nebulin: protein rulers in muscle? Trends in Biochem Sciences 19: 405–409

    Article  CAS  Google Scholar 

  • Trinick J (1996) Cytoskeleton — titin as a scaffold and a spring. Curr Biol 6:258–260

    Article  PubMed  CAS  Google Scholar 

  • Trombitas K & Pollack GH (1993) Elastic properties of the titin filament in the Z-line region of vertebrate striated muscle. J Muscle Res Cell Motil 14:416–422

    Article  PubMed  CAS  Google Scholar 

  • Tskhovrebova L & Trinick J (1997) Direct visualization of extensibility in isolated titin molecules. J Mol Biol 265:100–106

    Article  PubMed  CAS  Google Scholar 

  • Vigoreaux JO (1994) The muscle Z band: lessons in stress management. J Muscle Res Cell Motil 15:237–255

    PubMed  CAS  Google Scholar 

  • Vikstrom KL & Leinwand LA (1996) Contractile protein mutations and heart disease. Curr Opin Cell Biol 8:97–105

    Article  PubMed  CAS  Google Scholar 

  • Wallgren-Pettersson C, Avela K, Marchand S, Kolehmainen J, Tahvanainen E, Juul Hansen F, Muntoni F, Dubowitz V, de Visser M, Van Langen IM, Laing NG, Faure S & de la Chapelle A (1995) A gene for autosomal recessive nemaline myopathy assigned to chromosome 2q by linkage analysis. Neuromusc Disord 5:441–443

    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-Mitchell 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, McCarter R, Wright J, Beverly J & Ramirez-Mitchell R (1991) Regulation of skeletal muscle stiffness and elasticity by titin isoforms: A test of the segmental extension model of resting tension. Proc Natl Acad Sci USA 88:7101–7105

    Article  PubMed  CAS  Google Scholar 

  • Watkins H, Conner D, Thierfelder L, Jarcho JA, MacRae C, McKenna WJ, Maron BJ, Seidman JG & Seidman CE (1995) Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy. Nature Genet 11: 434–437

    Article  PubMed  CAS  Google Scholar 

  • Watkins H, Seidman JG & Seidman CE (1995) Familial hypertrophic cardiomyopathy: a genetic model of cardiac hypertrophy. Hum Mol Genet 4:1721–1727

    Article  PubMed  CAS  Google Scholar 

  • Whiting A, Wardale J & Trinick J (1989) Does titin regulate the length of muscle thick filaments? J Mol Biol 205:163–169

    Article  Google Scholar 

  • Yajima H, Ohtsuka H, Kawamura Y, Kume H, Murayama T, Abe H, Kimura S & Maruyama K (1996) A 11.5 kb 5′-terminal cDNA sequence of chicken breast muscle connectin/titin reveals its Z line binding region. Biochem Biophys Res Commun 223:160–164

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi M, Izumimoto M, Robson RM & Stromer MH (1985) Fine Structure of wide and narrow vertebrate muscle Z-lines. A proposed model and computer simulation of Z-line architecture. J Mol Biol 184:621–644

    Article  PubMed  CAS  Google Scholar 

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Kolmerer, B. et al. (1999). The titin cDNA sequence and partial genomic sequences: Insights into the molecular genetics, cell biology and physiology of the titin filament system. In: Reviews of Physiology, Biochemistry and Pharmacology. Reviews of Physiology, Biochemistry and Pharmacology, vol 138. Springer, Berlin, Heidelberg. https://doi.org/10.1007/BFb0119623

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