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Role of Titin in Skeletal Muscle Function and Disease

  • Coen A. C. Ottenheijm
  • Henk GranzierEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 682)

Abstract

This review covers recent developments in the titin field. Most recent reviews have discussed titin’s role in cardiac function: here we will mainly focus on skeletal muscle, and discuss recent advances in the understanding of titin’s role in skeletal muscle function and disease.

Keywords

Striated muscle Sarcomere PEVK Titin isoforms Single molecule 

References

  1. Bagnato P, Barone V, Giacomello E, Rossi D, Sorrentino V (2003) Binding of an ankyrin-1 ­isoform to obscurin suggests a molecular link between the sarcoplasmic reticulum and myofibrils in striated muscles. J Cell Biol 160(2):245–253PubMedCrossRefGoogle Scholar
  2. Bang ML, Centner T, Fornoff F, Geach AJ, Gotthardt M, McNabb M, Witt CC, Labeit D, Gregorio CC, Granzier H, Labeit S (2001) The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system. Circ Res 89(11):1065–1072PubMedCrossRefGoogle Scholar
  3. Barash IA, Mathew L, Lahey M, Greaser ML, Lieber RL (2005) Muscle LIM protein plays both structural and functional roles in skeletal muscle. Am J Physiol Cell Physiol 289(5):C1312–C1320PubMedCrossRefGoogle Scholar
  4. Barash IA, Bang ML, Mathew L, Greaser ML, Chen J, Lieber RL (2007) Structural and regulatory roles of muscle ankyrin repeat protein family in skeletal muscle. Am J Physiol Cell Physiol 293(1):C218–C227PubMedCrossRefGoogle Scholar
  5. Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K, Pan ZQ, Valenzuela DM, DeChiara TM, Stitt TN, Yancopoulos GD, Glass DJ (2001) Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294(5547):1704–1708PubMedCrossRefGoogle Scholar
  6. Cazorla O, Freiburg A, Helmes M, Centner T, McNabb M, Wu Y, Trombitas K, Labeit S, Granzier H (2000) Differential expression of cardiac titin isoforms and modulation of cellular stiffness. Circ Res 86(1):59–67PubMedCrossRefGoogle Scholar
  7. Cazorla O, Wu Y, Irving TC, Granzier H (2001) Titin-based modulation of calcium sensitivity of active tension in mouse skinned cardiac myocytes. Circ Res 88(10):1028–1035PubMedCrossRefGoogle Scholar
  8. Centner T, Yano J, Kimura E, McElhinny AS, Pelin K, Witt CC, Bang ML, Trombitas K, Granzier H, Gregorio CC, Sorimachi H, Labeit S (2001) Identification of muscle specific ring finger proteins as potential regulators of the titin kinase domain. J Mol Biol 306(4):717–726PubMedCrossRefGoogle Scholar
  9. Clarke BA, Drujan D, Willis MS, Murphy LO, Corpina RA, Burova E, Rakhilin SV, Stitt TN, Patterson C, Latres E, Glass DJ (2007) The E3 Ligase MuRF1 degrades myosin heavy chain protein in dexamethasone-treated skeletal muscle. Cell Metab 6 (5):376–385PubMedCrossRefGoogle Scholar
  10. Coen AC, Ottenheijm, Anna M. Knottnerus, Danielle Buck, Xiuju Luo, Kevin Greer, Adam Hoying, Siegfried Labeit, and Henk Granzier (2009) Tuning passive mechanics through differential splicing of titin During Skeletal Muscle Development. J Biol 97(8):2277–2286PubMedCrossRefGoogle Scholar
  11. Ehler E, Horowits R, Zuppinger C, Price RL, Perriard E, Leu M, Caroni P, Sussman M, Eppenberger HM, Perriard JC (2001) Alterations at the intercalated disk associated with the absence of muscle LIM protein. J Cell Biol 153(4):763–772PubMedCrossRefGoogle Scholar
  12. Erickson HP (1994) Reversible unfolding of fibronectin type III and immunoglobulin domains provides the structural basis for stretch and elasticity of titin and fibronectin. Proc Natl Acad Sci U S A 91(21):10114–10118PubMedCrossRefGoogle Scholar
  13. Freiburg A, Trombitas K, Hell W, Cazorla O, Fougerousse F, Centner T, Kolmerer B, Witt C, Beckmann JS, Gregorio CC, Granzier H, Labeit S. (2000) Series of exon-skipping events in the elastic spring region of titin as the structural basis for myofibrillar elastic diversity. Circ Res 86(11):1114–1121PubMedCrossRefGoogle Scholar
  14. Friden J, Lieber RL (2003) Spastic muscle cells are shorter and stiffer than normal cells. Muscle Nerve 27(2):157–164PubMedCrossRefGoogle Scholar
  15. Fukuda N, Wu Y, Farman G, Irving TC, Granzier H. (2003) Titin isoform variance and length dependence of activation in skinned bovine cardiac muscle. J Physiol 553. 1:147–154CrossRefGoogle Scholar
  16. Fukuzawa A, Lange S, Holt M, Vihola A, Carmignac V, Ferreiro A, Udd B, Gautel M (2008) Interactions with titin and myomesin target obscurin and obscurin-like 1 to the M-band: ­implications for hereditary myopathies. J Cell Sci 121:1841–1851PubMedCrossRefGoogle Scholar
  17. Furukawa T, Ono Y, Tsuchiya H, Katayama Y, Bang ML, Labeit D, Labeit S, Inagaki N, Gregorio CC (2001) Specific interaction of the potassium channel beta-subunit minK with the sarcomeric protein T-cap suggests a T-tubule-myofibril linking system. J Mol Biol. 313(4):775–784PubMedCrossRefGoogle Scholar
  18. Gautel M, Leonard K, Labeit S (1993) Phosphorylation of KSP motifs in the C-terminal region of titin in differentiating myoblasts. EMBO J 12(10):3827–3834PubMedGoogle Scholar
  19. Gerull B, Gramlich M, Atherton J, McNabb M, Trombitás K, Sasse-Klaassen S, Seidman JG, Seidman C, Granzier H, Labeit S, Frenneaux M, Thierfelder L (2002) Mutations of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy. Nat Genet 30(2):201–204PubMedCrossRefGoogle Scholar
  20. Gotthardt M, Hammer RE, Hübner N, Monti J, Witt CC, McNabb M, Richardson JA, Granzier H, Labeit S, Herz J (2003) Conditional expression of mutant M-line titins results in cardiomyopathy with altered sarcomere structure. J Biol Chem 278(8):6059–6065PubMedCrossRefGoogle Scholar
  21. Granzier H, Labeit S (2004) The giant protein titin: a major player in myocardial mechanics, signaling, and disease. Circ Res 94(3):284–295PubMedCrossRefGoogle Scholar
  22. Granzier H, Labeit S (2007) Structure-function relations of the giant elastic protein titin in striated and smooth muscle cells. Muscle & Nerve 36(6):740–755CrossRefGoogle Scholar
  23. Granzier H, Kellermayer M, Helmes M, Trombitás K (1997) Titin elasticity and mechanism of passive force development in rat cardiac myocytes probed by thin-filament extraction. Biophys J 73(4):2043–2053PubMedCrossRefGoogle Scholar
  24. Gregorio CC, Trombitás K, Centner T, Kolmerer B, Stier G, Kunke K, Suzuki K, Obermayr F, Herrmann B, Granzier H, Sorimachi H, Labeit S (1998) The NH2 terminus of titin spans the Z-disc: its interaction with a novel 19-kD ligand (T-cap) is required for sarcomeric integrity. J Cell Biol 143(4):1013–1027PubMedCrossRefGoogle Scholar
  25. Hackman P, Vihola A, Haravuori H, Marchand S, Sarparanta J, De Seze J, Labeit S, Witt C, Peltonen L, Richard I, Udd B (2002) Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin. Am J Hum Genet 71(3):492–500PubMedCrossRefGoogle Scholar
  26. Hackman P, Marchand S, Sarparanta J, Vihola A, Pénisson-Besnier I, Eymard B, Pardal-Fernández JM, Hammouda EL-H, Richard I, Illa I, Udd B (2008) Truncating mutations in C-terminal titin may cause more severe tibial muscular dystrophy (TMD). Neuromuscul Disord 18(12):922–928PubMedCrossRefGoogle Scholar
  27. Haravuori H, Vihola A, Straub V, Auranen M, Richard I, Marchand S, Voit T, Labeit S, Somer H, Peltonen L, Beckmann JS, Udd B (2001) Secondary calpain3 deficiency in 2q-linked muscular dystrophy: titin is the candidate gene. Neurology 56(7):869–877PubMedCrossRefGoogle Scholar
  28. Hayashi C, Ono Y, Doi N, Kitamura F, Tagami M, Mineki R, Arai T, Taguchi H, Yanagida M, Hirner S, Labeit D, Labeit S, Sorimachi H (2008) Multiple molecular interactions implicate the connectin/titin N2A region as a modulating scaffold for p94/calpain 3 activity in skeletal muscle. J Biol Chem 283(21):14801–14814PubMedCrossRefGoogle Scholar
  29. Helmes M, Trombitás K, Centner T, Kellermayer M, Labeit S, Linke WA, Granzier H (1999) Mechanically driven contour-length adjustment in rat cardiac titin’s unique N2B sequence: titin is an adjustable spring. Circ Res 84(11):1339–1352PubMedCrossRefGoogle Scholar
  30. Ikeda K, Yamamoto R, Wirschell M, Yagi T, Bower R, Porter ME, Sale WS, Kamiya R (2009) A novel ankyrin-repeat protein interacts with the regulatory proteins of inner arm dynein f (I1) of Chlamydomonas reinhardtii. Cell Motil Cytoskeleton 66(8):448–56PubMedCrossRefGoogle Scholar
  31. Kedar V, McDonough H, Arya R, Li HH, Rockman HA, Patterson C (2004) Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I. Proc Natl Acad Sci U S A 101(52):18135–18140PubMedCrossRefGoogle Scholar
  32. Kellermayer MS, Smith SB, Granzier HL, Bustamante C (1997) Folding-unfolding transitions in single titin molecules characterized with laser tweezers. Science 276 (5315):1112–1116PubMedCrossRefGoogle Scholar
  33. Kellermayer MS, Smith SB, Bustamante C, Granzier HL (2001) Mechanical fatigue in repetitively stretched single molecules of titin. Biophys J 80(2):852–863PubMedCrossRefGoogle Scholar
  34. Kemp TJ, Sadusky TJ, Saltisi F, Carey N, Moss J, Yang SY, Sassoon DA, Goldspink G, Coulton GR (2000) Identification of Ankrd2, a novel skeletal muscle gene coding for a stretch-responsive ankyrin-repeat protein. Genomics 66(3):229–241PubMedCrossRefGoogle Scholar
  35. Knöll 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 cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy. Cell 111(7):943–955PubMedCrossRefGoogle Scholar
  36. Krüger M, Kohl T, Linke WA (2006) Developmental changes in passive stiffness and myofilament Ca2+ sensitivity due to titin and troponin-I isoform switching are not critically triggered by birth. Am J Physiol Heart Circ Physiol 291(2):H496–H506PubMedCrossRefGoogle Scholar
  37. Krüger M, Sachse C, Zimmermann WH, Eschenhagen T, Klede S, Linke WA (2008) Thyroid hormone regulates developmental titin isoform transitions via the phosphatidylinositol-3-kinase/AKT pathway. Circ Res 102(4):439–447PubMedCrossRefGoogle Scholar
  38. Kulke M, Fujita-Becker S, Rostkova E, Neagoe C, Labeit D, Manstein DJ, Gautel M, Linke WA (2001) Interaction between PEVK-titin and actin filaments: origin of a viscous force component in cardiac myofibrils. Circ Res 89(10):874–881PubMedCrossRefGoogle Scholar
  39. Labeit S, Kolmerer B (1995) Titins: giant proteins in charge of muscle ultrastructure and elasticity. Science 270(5234):293–296PubMedCrossRefGoogle Scholar
  40. Labeit S, Kolmerer B, Linke WA (1997) The giant protein titin. Emerging roles in physiology and pathophysiology. Circ Res 80(2):290–294PubMedCrossRefGoogle Scholar
  41. Labeit D, Watanabe K, Witt C, Fujita H, Wu Y, Lahmers S, Funck T, Labeit S, Granzier H (2003) Calcium-dependent molecular spring elements in the giant protein titin. Proc Natl Acad Sci USA 100(23):13716–13721PubMedCrossRefGoogle Scholar
  42. Lahmers S, Wu Y, Call DR, Labeit S, Granzier H (2004) Developmental control of titin isoform expression and passive stiffness in fetal and neonatal myocardium. Circ Res 94(4):505–513PubMedCrossRefGoogle Scholar
  43. Lange S, Xiang F, Yakovenko A, Vihola A, Hackman P, Rostkova E, Kristensen J, Brandmeier B, Franzen G, Hedberg B, Gunnarsson LG, Hughes SM, Marchand S, Sejersen T, Richard I, Edström L, Ehler E, Udd B, Gautel M (2005) The kinase domain of titin controls muscle gene expression and protein turnover. Science 308 (5728):1599–1603PubMedCrossRefGoogle Scholar
  44. Leake MC, Wilson D, Gautel M, Simmons RM (2004) The elasticity of single titin molecules using a two-bead optical tweezers assay. Biophys J 87(2):1112–1135PubMedCrossRefGoogle Scholar
  45. Leake MC, Grützner A, Krüger M, Linke WA (2006) Mechanical properties of cardiac titin’s N2B-region by single-molecule atomic force spectroscopy. J Struct Biol 155(2):263–272PubMedCrossRefGoogle Scholar
  46. LeWinter MM, Wu Y, Labeit S, Granzier H (2007) Cardiac titin: structure, functions and role in disease. Clin Chim Acta 375(1–2):1–9PubMedCrossRefGoogle Scholar
  47. Li H, Fernandez JM (2003) Mechanical design of the first proximal Ig domain of human cardiac titin revealed by single molecule force spectroscopy. J Mol Biol 334(1):75–86PubMedCrossRefGoogle Scholar
  48. Li H, Oberhauser AF, Redick SD, Carrion-Vazquez M, Erickson HP, Fernandez JM (2001) Multiple conformations of PEVK proteins detected by single-molecule techniques. Proc Natl Acad Sci USA 98(19):10682–10686PubMedCrossRefGoogle Scholar
  49. Li H, Linke WA, Oberhauser AF, Carrion-Vazquez M, Kerkvliet JG, Lu H, Marszalek PE, Fernandez JM (2002) Reverse engineering of the giant muscle protein titin. Nature 418(6901):998–1002PubMedCrossRefGoogle Scholar
  50. Linke WA (2008) Sense and stretchability: the role of titin and titin-associated proteins in ­myocardial stress-sensing and mechanical dysfunction. Cardiovasc Res 77(4):637–648PubMedGoogle Scholar
  51. Linke WA, Ivemeyer M, Mundel P, Stockmeier MR, Kolmerer B (1998) Nature of PEVK-titin elasticity in skeletal muscle. Proc Natl Acad Sci U S A 95(14):8052–8057PubMedCrossRefGoogle Scholar
  52. Linke WA, Rudy DE, Centner T, Gautel M, Witt C, Labeit S, Gregorio CC (1999) I-band titin in cardiac muscle is a three-element molecular spring and is critical for maintaining thin filament structure. J Cell Biol 146(3):631–644PubMedCrossRefGoogle Scholar
  53. Liversage AD, Holmes D, Knight PJ, Tskhovrebova L, Trinick J (2001) Titin and the sarcomere symmetry paradox. J Mol Biol 305(3):401–409PubMedCrossRefGoogle Scholar
  54. Mancini DM, Henson D, LaManca J, Levine S (1992) Respiratory muscle function and dyspnea in patients with chronic congestive heart failure. Circulation 86(3):909–918PubMedCrossRefGoogle Scholar
  55. Maruyama K (1976) Connectin, an elastic protein from myofibrils. J Biochem 80(2):405–407PubMedGoogle Scholar
  56. Mayans O, van der Ven PF, Wilm M, Mues A, Young P, Fürst DO, Wilmanns M, Gautel M (1998) Structural basis for activation of the titin kinase domain during myofibrillogenesis. Nature 395(6705):863–869PubMedCrossRefGoogle Scholar
  57. Miller MK, Bang ML, Witt CC, Labeit D, Trombitas C, Watanabe K, Granzier H, McElhinny AS, Gregorio CC, Labeit S (2003) The muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP as a family of titin filament-based stress response molecules. J Mol Biol 333(5):951–964PubMedCrossRefGoogle Scholar
  58. Minajeva A, Kulke M, Fernandez JM, Linke WA (2001) Unfolding of titin domains explains the viscoelastic behavior of skeletal myofibrils. Biophys J 80(3):1442–1451PubMedCrossRefGoogle Scholar
  59. Moore AJ, Stubbings A, Swallow EB, Dusmet M, Goldstraw P, Porcher R, Moxham J, Polkey MI, Ferenczi MA (2006) Passive properties of the diaphragm in COPD. J Appl Physiol 101(5):1400–1405PubMedCrossRefGoogle Scholar
  60. Mrosek M, Labeit D, Witt S, Heerklotz H, von Castelmur E, Labeit S, Mayans O (2007) Molecular determinants for the recruitment of the ubiquitin-ligase MuRF-1 onto M-line titin. FASEB J 21(7):1383–1392PubMedCrossRefGoogle Scholar
  61. Mues A, van der Ven PF, Young P, Fürst DO, Gautel M (1998) Two immunoglobulin-like domains of the Z-disc portion of titin interact in a conformation-dependent way with telethonin. FEBS Lett 428(1–2):111–114PubMedCrossRefGoogle Scholar
  62. Mutungi G, Trinick J, Ranatunga KW (2003) Resting tension characteristics in differentiating intact rat fast- and slow-twitch muscle fibers. J Appl Physiol 95(6):2241–2247PubMedGoogle Scholar
  63. Nagy A, Grama L, Huber T, Bianco P, Trombitás K, Granzier HL, Kellermayer MS (2005) Hierarchical extensibility in the PEVK domain of skeletal-muscle titin. Biophys J 89(1):329–336PubMedCrossRefGoogle Scholar
  64. Nakada C, Oka A, Nonaka I, Sato K, Mori S, Ito H, Moriyama M (2003) Cardiac ankyrin repeat protein is preferentially induced in atrophic myofibers of congenital myopathy and spinal muscular atrophy. Pathol Int 53(10):653–658PubMedCrossRefGoogle Scholar
  65. Obermann WM, Gautel M, Steiner F, van der Ven PF, 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(6):1441–1453PubMedCrossRefGoogle Scholar
  66. Obermann WM, Gautel M, Weber K, Fürst DO (1997) Molecular structure of the sarcomeric M band: mapping of titin and myosin binding domains in myomesin and the identification of a potential regulatory phosphorylation site in myomesin. EMBO J 16(2):211–220PubMedCrossRefGoogle Scholar
  67. Olsson MC, Krüger M, Meyer LH, Ahnlund L, Gransberg L, Linke WA, Larsson L (2006) Fibre type-specific increase in passive muscle tension in spinal cord-injured subjects with spasticity. J Physiol 577.1:339–352PubMedCrossRefGoogle Scholar
  68. Omens JH, Usyk TP, Li Z, McCulloch AD (2002) Muscle LIM protein deficiency leads to alterations in passive ventricular mechanics. Am J Physiol Heart Circ Physiol 282(2):H680–H687PubMedGoogle Scholar
  69. Ono Y, Kakinuma K, Torii F, Irie A, Nakagawa K, Labeit S, Abe K, Suzuki K, Sorimachi H (2004) Possible regulation of the conventional calpain system by skeletal muscle-specific calpain, p94/calpain 3. J Biol Chem 279(4):2761–2771PubMedCrossRefGoogle Scholar
  70. Ottenheijm CA, Heunks LM, Hafmans T, van der Ven PF, Benoist C, Zhou H, Labeit S, Granzier HL, Dekhuijzen PN (2006) Titin and diaphragm dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 173(5):527–534PubMedCrossRefGoogle Scholar
  71. Ottenheijm CA, Heunks LM, Dekhuijzen PN (2007) Diaphragm muscle fiber dysfunction in chronic obstructive pulmonary disease: toward a pathophysiological concept. Am J Respir Crit Care Med 175(12):1233–1240PubMedCrossRefGoogle Scholar
  72. Prado LG, Makarenko I, Andresen C, Krüger M, Opitz CA, Linke WA (2005) Isoform diversity of giant proteins in relation to passive and active contractile properties of rabbit skeletal muscles. J Gen Physiol 126(5):461–480PubMedCrossRefGoogle Scholar
  73. Puchner EM, Alexandrovich A, Kho AL, Hensen U, Schäfer LV, Brandmeier B, Gräter F, Grubmüller H, Gaub HE, Gautel M (2008) Mechanoenzymatics of titin kinase. Proc Natl Acad Sci U S A 105(36):13385–13390PubMedCrossRefGoogle Scholar
  74. Raynaud F, Fernandez E, Coulis G, Aubry L, Vignon X, Bleimling N, Gautel M, Benyamin Y, Ouali A (2005) Calpain 1-titin interactions concentrate calpain 1 in the Z-band edges and in the N2-line region within the skeletal myofibril. FEBS J 272(10):2578–2590PubMedCrossRefGoogle Scholar
  75. Rief M, Gautel M, Oesterhelt F, Fernandez JM, Gaub HE (1997) Reversible unfolding of individual titin immunoglobulin domains by AFM. Science 276(5315):1109–1112PubMedCrossRefGoogle Scholar
  76. Russell MW et al. (2002) Identification, tissue expression and chromosomal localization of human Obscurin-MLCK, a member of the titin and Dbl families of myosin light chain kinases. Gene 282 (1–2):237–246PubMedCrossRefGoogle Scholar
  77. Sarkar A, Caamano S, and Fernandez JM (2005) The elasticity of individual titin PEVK exons measured by single molecule atomic force microscopy. J Biol Chem 280 (8):6261–6264PubMedCrossRefGoogle Scholar
  78. Toursel T, Stevens L, Granzier H, Mounier Y (2002) Passive tension of rat skeletal soleus muscle fibers: effects of unloading conditions. J Appl Physiol 92(4):1465–1472PubMedGoogle Scholar
  79. Trombitás K, Greaser M, French G, Granzier H (1998a) PEVK extension of human soleus muscle titin revealed by immunolabeling with the anti-titin antibody 9D10. J Struct Biol 122(1–2):188–196PubMedCrossRefGoogle Scholar
  80. Trombitás K, Greaser M, Labeit S, Jin JP, Kellermayer M, Helmes M, Granzier H (1998b) Titin extensibility in situ: entropic elasticity of permanently folded and permanently unfolded molecular segments. J Cell Biol 140(4):853–859PubMedCrossRefGoogle Scholar
  81. Trombitás K, Freiburg A, Centner T, Labeit S, Granzier H (1999) Molecular dissection of N2B cardiac titin’s extensibility. Biophys J 77(6):3189–3196PubMedCrossRefGoogle Scholar
  82. Trombitás K, Wu Y, Labeit D, Labeit S, Granzier H (2001) Cardiac titin isoforms are coexpressed in the half-sarcomere and extend independently. Am J Physiol Heart Circ Physiol 281(4):H1793–H1799PubMedGoogle Scholar
  83. Trombitás K, Wu Y, McNabb M, Greaser M, Kellermayer MS, Labeit S, Granzier H (2003) Molecular basis of passive stress relaxation in human soleus fibers: assessment of the role of immunoglobulin-like domain unfolding. Biophys J 85(5):3142–3153PubMedCrossRefGoogle Scholar
  84. Tskhovrebova L, Trinick J, Sleep JA, Simmons RM (1997) Elasticity and unfolding of single molecules of the giant muscle protein titin. Nature 387(6630):308–312PubMedCrossRefGoogle Scholar
  85. Udaka J, Ohmori S, Terui T, Ohtsuki I, Ishiwata S, Kurihara S, Fukuda N (2008) Disuse-induced preferential loss of the giant protein titin depresses muscle performance via abnormal sarcomeric organization. J Gen Physiol 131(1):33–41PubMedCrossRefGoogle Scholar
  86. Van den Bergh PY, Bouquiaux O, Verellen C, Marchand S, Richard I, Hackman P, Udd B (2003) Tibial muscular dystrophy in a Belgian family. Ann Neurol 54(2):248–251PubMedCrossRefGoogle Scholar
  87. van Hees HW, Ottenheijm CA, Granzier HL, Dekhuijzen PN, Heunks LM (2010) Int J Cardiol. 141(3):275–283PubMedCrossRefGoogle Scholar
  88. Wang K, McClure J, Tu A (1979) Titin: major myofibrillar components of striated muscle. Proc Natl Acad Sci USA 76(8):3698–3702PubMedCrossRefGoogle Scholar
  89. Warren CM, Krzesinski PR, Campbell KS, Moss RL, Greaser ML (2004) Titin isoform changes in rat myocardium during development. Mech Dev 121(11):1301–1312PubMedCrossRefGoogle Scholar
  90. Watanabe K, Muhle-Goll C, Kellermayer MS, Labeit S, Granzier H (2002a) Different molecular mechanics displayed by titin’s constitutively and differentially expressed tandem Ig segments. J Struct Biol 137(1–2):248–258PubMedCrossRefGoogle Scholar
  91. Watanabe K, Nair P, Labeit D, Kellermayer MS, Greaser M, Labeit S, Granzier H (2002b) Molecular mechanics of cardiac titin’s PEVK and N2B spring elements. J Biol Chem 277(13):11549–11558PubMedCrossRefGoogle Scholar
  92. Weinert S, Bergmann N, Luo X, Erdmann B, Gotthardt M (2006) M line-deficient titin causes cardiac lethality through impaired maturation of the sarcomere. J Cell Biol 173(4):559–570PubMedCrossRefGoogle Scholar
  93. Witt CC, Ono Y, Puschmann E, McNabb M, Wu Y, Gotthardt M, Witt SH, Haak M, Labeit D, Gregorio CC, Sorimachi H, Granzier H, Labeit S (2004) Induction and myofibrillar targeting of CARP, and suppression of the Nkx2.5 pathway in the MDM mouse with impaired titin-based signaling. J Mol Biol 336(1):145–154PubMedCrossRefGoogle Scholar
  94. Yamasaki R, Berri M, Wu Y, Trombitás K, McNabb M, Kellermayer MS, Witt C, Labeit D, Labeit S, Greaser M, Granzier H (2001) Titin-actin interaction in mouse myocardium: passive tension modulation and its regulation by calcium/S100A1. Biophys J 81(4):2297–2313PubMedCrossRefGoogle Scholar
  95. Young P, Ehler E, Gautel M (2001) Obscurin, a giant sarcomeric Rho guanine nucleotide exchange factor protein involved in sarcomere assembly. J Cell Biol 154(1):123–136PubMedCrossRefGoogle Scholar
  96. Zhu Y, Bogomolovas J, Labeit S, Granzier H (2009) Single molecule force spectroscopy of the cardiac titin N2B element: effects of the molecular chaperone alphaB-crystallin with ­disease-causing mutations. J Biol Chem 284(20):13914–13923PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of PhysiologyUniversity of ArizonaTucsonUSA

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