Thin filament mutations: Developing an integrative approach to a complex disorder

Circulation Research

Volumn 108, Issue 6, 2011, Pages 765-782

  Tardiff, Jil C ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

Ca2+kinetics; familial cardiomyopathy; thin filaments

Indexed keywords

ACTIN; ALPHA TROPOMYOSIN; TROPONIN T;

AMINO TERMINAL SEQUENCE; ARTICLE; CARDIOMYOPATHY; CONGESTIVE CARDIOMYOPATHY; DISEASE COURSE; GENE MUTATION; GENOTYPE PHENOTYPE CORRELATION; HEART CONTRACTION; HEART LEFT VENTRICLE HYPERTROPHY; HEART VENTRICLE REMODELING; HUMAN; HYPERTROPHIC CARDIOMYOPATHY; MYOFILAMENT; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; SARCOMERE; SUDDEN DEATH; THIN FILAMENT;

ANIMALS; CALCIUM; CARDIOMYOPATHY, HYPERTROPHIC, FAMILIAL; GENOTYPE; HUMANS; KINETICS; MICROFILAMENTS; MUTATION; MYOCARDIUM; PHENOTYPE; TROPOMYOSIN; TROPONIN;

EID: 79953055654     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.110.224170     Document Type: Article

References (129)

1. Geisterfer-Lowrance AA, Kass S, Tanigawa G, Vosberg HP, McKenna W, Seidman CE, Seidman JG. A molecular basis for familial hyper-trophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell. 1990;62:999-1006.
2. Teare D. Asymmetrical hypertrophy of the heart in young adults. Br Heart J. 1958;20:1-8.
3. Solomon SD, Jarcho JA, McKenna W, Geisterfer-Lowrance A, Germain R, Salerni R, Seidman JG, Seidman CE. Familial hypertrophic cardio-myopathy is a genetically heterogeneous disease. J Clin Invest. 1990; 86:993-999. (Pubitemid 20327393)
4. Thierfelder L, Watkins H, MacRae C, Lamas R, McKenna W, Vosberg HP, Seidman JG, Seidman CE. Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. Cell. 1994;77:701-712.
5. Kimura A, Harada H, Park JE, Nishi H, Satoh M, Takahashi M, Hiroi S, Sasaoka T, Ohbuchi N, Nakamura T, Koyanagi T, Hwang TH, Choo JA, Chung KS, Hasegawa A, Nagai R, Okazaki O, Nakamura H, Matsuzaki M, Sakamoto T, Toshima H, Koga Y, Imaizumi T, Sasazuki T. Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy. Nature. 1997;16:379-382. (Pubitemid 27323305)
6. Olson TM, Doan TP, Kishimoto NY, Whitby FG, Ackerman MJ, Fananapazir L. Inherited and de novo mutations in the cardiac actin gene cause hypertrophic cardiomyopathy. J Mol Cell Cardiol. 2000;32: 1687-1694.
7. Landstrom AP, Parvatiyar MS, Pinto JR, Marquardt ML, Bos JM, Tester DJ, Ommen SR, Potter JD, Ackerman MJ. Molecular and functional characterization of novel hypertrophic cardiomyopathy susceptibility mutations in TNNC1-encoded troponin C. J Mol Cell Cardiol. 2008;45: 281-288.
8. Frank S, Braunwald E. Idiopathic hypertrophic subaortic stenosis. Clinical analysis of 126 patients with emphasis on the natural history. Circulation. 1968;37:759-788.
9. Spirito P, Maron BJ. Relation between extent of left ventricular hypertrophy and diastolic filling abnormalities in hypertrophic cardiomyopa-thy. J Am Coll Cardiol. 1990;15:808-813. (Pubitemid 20101571)
10. Maron BJ, Bonow RO, Cannon RO III, Leon MB, Epstein SE. Hyper-trophic cardiomyopathy. Interrelations of clinical manifestations, patho-physiology, and therapy (1). N Engl J Med. 1987;316:780-789. (Pubitemid 17046087)
11. Richard P, Charron P, Carrier L, Ledeuil C, Cheav T, Pichereau C, Benaiche A, Isnard R, Dubourg O, Burban M, Gueffet JP, Millaire A, Desnos M, Schwartz K, Hainque B, Komajda M. Hypertrophic cardio-myopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Circulation. 2003;107: 2227-2232. (Pubitemid 36547217)
12. Kamisago M, Sharma SD, DePalma SR, Solomon S, Sharma P, McDonough B, Smoot L, Mullen MP, Woolf PK, Wigle ED, Seidman JG, Seidman CE. Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy. N Engl J Med. 2000;343:1688-1696.
13. Mogensen J, Kubo T, Duque M, Uribe W, Shaw A, Murphy R, Gimeno JR, Elliott P, McKenna WJ. Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations. J Clin Invest. 2003;111:209-216. (Pubitemid 36105919)
14. Kubo T, Gimeno JR, Bahl A, Steffensen U, Steffensen M, Osman E, Thaman R, Mogensen J, Elliott PM, Doi Y, McKenna WJ. Prevalence, clinical significance, and genetic basis of hypertrophic cardiomyopathy with restrictive phenotype. J Am Coll Cardiol. 2007;49:2419-2426. (Pubitemid 46962256)
15. Elliott P, McKenna WJ. How should hypertrophic cardiomyopathy be classified? Molecular diagnosis for hypertrophic cardiomyopathy: not ready for prime time. Circ Cardiovasc Genet. 2009;2:87-89.
16. Ingles J, Doolan A, Chiu C, Seidman J, Seidman C, Semsarian C. Compound and double mutations in patients with hypertrophic cardio-myopathy: implications for genetic testing and counselling. J Med Genet. 2005;42:e59.
17. Revera M, van der Merwe L, Heradien M, Goosen A, Corfield VA, Brink PA, Moolman-Smook JC. Long-term follow-up of R403W MYH7 and R92W TNNT2 HCM families: mutations determine left ventricular dimensions but not wall thickness during disease progression. Cardiovasc J Afr. 2007;18:146-153.
18. Ho CY, Lopez B, Coelho-Filho OR, Lakdawala NK, Cirino AL, Jarolim P, Kwong R, Gonzalez A, Colan SD, Seidman JG, Diez J, Seidman CE. Myocardial fibrosis as an early manifestation of hypertrophic cardiomy-opathy. N Engl J Med. 2010;363:552-563.
19. Cooke R. Actomyosin interaction in striated muscle. Physiol Rev. 1997; 77:671-697. (Pubitemid 27328737)
20. Takano M, Terada TP, Sasai M. Unidirectional brownian motion observed in an in silico single molecule experiment of an actomyosin motor. Proc Natl Acad Sci USA. 2010;107:7769-7774.
21. Solaro RJ, Rarick HM. Troponin and tropomyosin: proteins that switch on and tune in the activity of cardiac myofilaments. Circ Res. 1998;83: 471-480. (Pubitemid 28411048)
22. Ebashi S, Kodama A, Ebashi F. Troponin 1. Preparation and physiological function. J Biochem. 1968;64:465-477.
23. Hitchcock SE, Huxley HE, Szent-Gyorgyi AG. Calcium sensitive binding of troponin to actin-tropomyosin: a two-site model for troponin action. J Mol Biol. 1973;80:825-836.
24. McKillop DF, Geeves MA. Regulation of the interaction between actin and myosin subfragment 1: evidence for three states of the thin filament. Biophys J. 1993;65:693-701. (Pubitemid 23263882)
25. Pirani A, Vinogradova MV, Curmi PMG, King WA, Fletterick RJ, Craig R, Tobacman LS, Xu C, Hatch V, Lehman W. An atomic model of the thin filament in the relaxed and Ca2 +-activated states. J Mol Biol. 2006;357:707-717.
26. Lin D, Bobkova A, Homsher E, Tobacman LS. Altered cardiac troponin T in vitro function in the presence of a mutation implicated in familial hypertrophic cardiomyopathy. J Clin Invest. 1996;97:2842-2848. (Pubitemid 26197097)
27. Morimoto S, Yanaga F, Minakami R, Ohtsuki I. Ca2 +-sensitizing effects of the mutations at Ile-79 and Arg-92 of troponin T in hypertrophic cardiomyopathy. Am J Physiol. 1998;275:C200-C207.
28. Redwood C, Lohmann K, Bing W, Esposito GM, Elliott K, Abdulrazzak H, Knott A, Purcell I, Marston S, Watkins H. Investigation of a truncated cardiac troponin T that causes familial hypertrophic cardiomyopathy: Ca(2 +) regulatory properties of reconstituted thin filaments depend on the ratio of mutant to wild-type protein. Circ Res. 2000;86:1146-1152. (Pubitemid 30396040)
29. Gordon AM, Homsher E, Regnier M. Regulation of contraction in striated muscle. Physiol Rev. 2000;80:853-924. (Pubitemid 30164950)
30. Takeda S, Yamashita A, Maeda K, Maeda Y. Structure of the core domain of human cardiac troponin in the Ca(2 + )-saturated form. Nature. 2003;424:35-41. (Pubitemid 36834832)
31. Galińska-Rakoczy A, Engel P, Xu C, Jung H, Craig R, Tobacman LS, Lehman W. Structural basis for the regulation of muscle contraction by troponin and tropomyosin. J Mol Biol. 2008;379:929-935. (Pubitemid 351734500)
32. Saen-Oon S, Quaytman-Machleder S, Schramm VL, Schwartz SD. Atomic detail of chemical transformation at the transition state of an enzymatic reaction. Proc Natl Acad Sci USA. 2008;105:16543-16548.
33. Nashine VC, Hammes-Schiffer S, Benkovic SJ. Coupled motions in enzyme catalysis. Curr Opin Chem Biol. 2010;14:644-651.
34. Ertz-Berger BR, He H, Dowell C, Factor SM, Haim TE, Nunez S, Schwartz SD, Ingwall JS, Tardiff JC. Changes in the chemical and dynamic properties of cardiac troponin t cause discrete cardiomyopathies in transgenic mice. Proc Natl Acad Sci USA. 2005;102: 18219-18224. (Pubitemid 41798528)
35. Guinto P, Manning E, Schwartz SD, Tardiff JC. Computational characterization of mutations in cardiac troponin T known to cause familial hypertrophic cardiomyopathy. J Theor Comput Chem. 2007;6:413-419.
36. Lim CC, Yang H, Yang M, Wang CK, Shi J, Berg EA, Pimentel DR, Gwathmey JK, Hajjar RJ, Helmes M, Costello CE, Huo S, Liao R. A novel mutant cardiac troponin C disrupts molecular motions critical for calcium binding affinity and cardiomyocyte contractility. Biophys J. 2008;94:3577-3589.
37. Kokado H, Shimizu M, Yoshio H, Ino H, Okeie K, Emoto Y, Mat-suyama T, Yamaguchi M, Yasuda T, Fujino N, Ito H, Mabuchi H. Clinical features of hypertrophic cardiomyopathy caused by a Lys183 deletion mutation in the cardiac troponin I gene. Circulation. 2000;102: 663-669. (Pubitemid 30640667)
38. Kaski JP, Syrris P, Burch M, Tome-Esteban MT, Fenton M, Christiansen M, Andersen PS, Sebire N, Ashworth M, Deanfield JE, McKenna WJ, Elliott PM. Idiopathic restrictive cardiomyopathy in children is caused by mutations in cardiac sarcomere protein genes. Heart. 2008;94:1478-1484.
39. Mogensen J, Murphy RT, Kubo T, Bahl A, Moon JC, Klausen IC, Elliott PM, McKenna WJ. Frequency and clinical expression of cardiac troponin I mutations in 748 consecutive families with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2004;44:2315-2325. (Pubitemid 39647604)
40. Carballo S, Robinson P, Otway R, Fatkin D, Jongbloed JDH, de Jonge N, Blair E, van Tintelen JP, Redwood C, Watkins H. Identification and functional characterization of cardiac troponin I as a novel disease gene in autosomal dominant dilated cardiomyopathy. Circ Res. 2009;105: 375-382.
41. Hoffman RM, Sykes BD. Disposition and dynamics: interdomain orientations in troponin. Adv Exp Med Biol. 2007;592:59-70.
42. Frazier A, Judge DP, Schulman SP, Johnson N, Holmes KW, Murphy AM. Familial hypertrophic cardiomyopathy associated with cardiac beta-myosin heavy chain and troponin I mutations. Pediatr Cardiol. 2008;29:846-850.
43. Elliott K, Watkins H, Redwood CS. Altered regulatory properties of human cardiac troponin I mutants that cause hypertrophic cardiomyopathy. J Biol Chem. 2000;275:22069-22074. (Pubitemid 30621785)
44. Takahashi-Yanaga F, Morimoto S, Harada K, Minakami R, Shiraishi F, Ohta M, Lu QW, Sasaguri T, Ohtsuki I. Functional consequences of the mutations in human cardiac troponin I gene found in familial hypertrophic cardiomyopathy. J Mol Cell Cardiol. 2001;33:2095-2107. (Pubitemid 34073053)
45. James J, Zhang Y, Osinska H, Sanbe A, Klevitsky R, Hewett TE, Robbins J. Transgenic modeling of a cardiac troponin I mutation linked to familial hypertrophic cardiomyopathy. Circ Res. 2000;87:805-811.
46. Kobayashi, Solaro R. Increased Ca2 + affinity of cardiac thin filaments reconstituted with cardiomyopathy-related mutant cardiac troponin I. J Biol Chem. 2006;281:13471-13477.
47. Galińska A, Hatch V, Craig R, Murphy AM, Van Eyk JE, Wang C-LA, Lehman W, Foster DB. The C terminus of cardiac troponin I stabilizes the Ca2 +-activated state of tropomyosin on actin filaments. Circ Res. 2010;106:705-711.
48. Hoffman RM, Blumenschein TM, Sykes BD. An interplay between protein disorder and structure confers the Ca2 + regulation of striated muscle. J Mol Biol. 2006;361:625-633. (Pubitemid 44175378)
49. Mathur MC, Kobayashi T, Chalovich JM. Negative charges at protein kinase C sites of troponin I stabilize the inactive state of actin. Biophys J. 2008;94:542-549.
50. Metzger JM, Westfall MV. Covalent and noncovalent modification of thin filament action: the essential role of troponin in cardiac muscle regulation. Circ Res. 2004;94:146-158. (Pubitemid 38197446)
51. Deng Y, Schmidtmann A, Redlich A, Westerdorf B, Jaquet K, Thieleczek R. Effects of phosphorylation and mutation R145G on human cardiac troponin I function. Biochemistry. 2001;40: 14593-14602. (Pubitemid 33111743)
52. Deng Y, Schmidtmann A, Kruse S, Filatov V, Heilmeyer LMG, Jaquet K, Thieleczek R. Phosphorylation of human cardiac troponin I G203S and K206Q linked to familial hypertrophic cardiomyopathy affects acto-myosin interaction in different ways. J Mol Cell Cardiol. 2003;35: 1365-1374. (Pubitemid 37330094)
53. Gomes AV, Harada K, Potter JD. A mutation in the N-terminus of troponin I that is associated with hypertrophic cardiomyopathy affects the Ca(2 + )-sensitivity, phosphorylation kinetics and proteolytic susceptibility of troponin. J Mol Cell Cardiol. 2005;39:754-765. (Pubitemid 41464412)
54. Kobayashi T, Solaro RJ. Calcium, thin filaments, and the integrative biology of cardiac contractility. Annu Rev Physiol. 2005;67:39-67. (Pubitemid 40404485)
55. Howarth JW, Meller J, Solaro RJ, Trewhella J, Rosevear PR. Phosphorylation-dependent conformational transition of the cardiac specific N-extension of troponin I in cardiac troponin. J Mol Biol. 2007;373: 706-722. (Pubitemid 47488403)
56. Mogensen J, Murphy RT, Shaw T, Bahl A, Redwood C, Watkins H, Burke M, Elliott PM, McKenna WJ. Severe disease expression of cardiac troponin C and T mutations in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 2004;44:2033-2040. (Pubitemid 39473290)
57. Lakdawala NK, Dellefave L, Redwood CS, Sparks E, Cirino AL, Depalma S, Colan SD, Funke B, Zimmerman RS, Robinson P, Watkins H, Seidman CE, Seidman JG, McNally EM, Ho CY. Familial dilated cardiomyopathy caused by an alpha-tropomyosin mutation: the distinctive natural history of sarcomeric dilated cardiomyopathy. J Am Coll Cardiol. 2010;55:320-329.
58. Preston LC, Lipscomb S, Robinson P, Mogensen J, McKenna WJ, Watkins H, Ashley CC, Redwood CS. Functional effects of the DCM mutant Gly159Asp troponin C in skinned muscle fibres. Pflugers Arch. 2007;453:771-776. (Pubitemid 46294929)
59. Biesiadecki BJ, Kobayashi T, Walker JS, John Solaro R, de Tombe PP. The troponin C G159D mutation blunts myofilament desensitization induced by troponin I Ser23/24 phosphorylation. Circ Res. 2007;100: 1486-1493. (Pubitemid 46834761)
60. Dyer EC, Jacques AM, Hoskins AC, Ward DG, Gallon CE, Messer AE, Kaski JP, Burch M, Kentish JC, Marston SB. Functional analysis of a unique troponin C mutation, Gly159Asp, that causes familial dilated cardiomyopathy, studied in explanted heart muscle. Circ Heart Fail. 2009;2:456-464.
61. Tobacman LS. Thin filament-mediated regulation of cardiac contraction. Ann Rev Physiol. 1996;58:447-481. (Pubitemid 26106729)
62. Watkins H, McKenna WJ, Thierfelder L, Suk HJ, Anan R, O'Donoghue A, Spirito P, Matsumori A, Moravec CS, Seidman JG. Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy. N Engl J Med. 1995;332:1058-1064.
63. Van Driest SL, Ackerman MJ, Ommen SR, Shakur R, Will ML, Nishimura RA, Tajik AJ, Gersh BJ. Prevalence and severity of "benign" mutations in the beta-myosin heavy chain, cardiac troponin T, and alpha-tropomyosin genes in hypertrophic cardiomyopathy. Circulation. 2002;106:3085-3090. (Pubitemid 35440293)
64. Moolman JC, Corfield VA, Posen B, Ngumbela K, Seidman C, Brink PA, Watkins H. Sudden death due to troponin T mutations. J Am Coll Cardiol. 1997;29:549-555. (Pubitemid 27116096)
65. Varnava AM, Elliott PM, Baboonian C, Davison F, Davies MJ, McKenna WJ. Hypertrophic cardiomyopathy: histopathological features of sudden death in cardiac troponin T disease. Circulation. 2001;104: 1380-1384. (Pubitemid 32880150)
66. Van Driest SL, Ellsworth EG, Ommen SR, Tajik AJ, Gersh BJ, Ackerman MJ. Prevalence and spectrum of thin filament mutations in an outpatient referral population with hypertrophic cardiomyopathy. Circulation. 2003;108:445-451. (Pubitemid 36935538)
67. Menon SC, Michels VV, Pellikka PA, Ballew JD, Karst ML, Herron KJ, Nelson SM, Rodeheffer RJ, Olson TM. Cardiac troponin T mutation in familial cardiomyopathy with variable remodeling and restrictive physiology. Clin Genet. 2008;74:445-454.
68. Li D, Czernuszewicz GZ, Gonzalez O, Tapscott T, Karibe A, Durand JB, Brugada R, Hill R, Gregoritch JM, Anderson JL, Quinones M, Bachinski LL, Roberts R. Novel cardiac troponin T mutation as a cause of familial dilated cardiomyopathy. Circulation. 2001;104:2188-2193. (Pubitemid 33043298)
69. Ohtsuki I. Molecular arrangement of troponin-T in the thin filament. J Biochem. 1979;86:491-497. (Pubitemid 10251093)
70. Hershberger RE, Pinto JR, Parks SB, Kushner JD, Li D, Ludwigsen S, Cowan J, Morales A, Parvatiyar MS, Potter JD. Clinical and functional characterization of TNNT2 mutations identified in patients with dilated cardiomyopathy. Circ Cardiovasc Genet. 2009;2:306-313.
71. Forissier JF, Carrier L, Farza H, Bonne G, Bercovici J, Richard P, Hainque B, Townsend PJ, Yacoub MH, Faure S, Dubourg O, Millaire A, Hagege AA, Desnos M, Komajda M, Schwartz K. Codon 102 of the cardiac troponin T gene is a putative hot spot for mutations in familial hypertrophic cardiomyopathy. Circulation. 1996;94:3069-3073. (Pubitemid 26427467)
72. Heald RW, Hitchcock-DeGregori SE. The structure of the amino terminus of tropomyosin is critical for binding to actin in the absence and presence of troponin. J Biol Chem. 1988;263:5254-5259.
73. Hinkle A, Goranson A, Butters CA, Tobacman LS. Roles for the troponin tail domain in thin filament assembly and regulation. A dele-tional study of cardiac troponin T. J Biol Chem. 1999;274:7157-7164.
74. Tobacman LS, Nihli M, Butters C, Heller M, Hatch V, Craig R, Lehman W, Homsher E. The troponin tail domain promotes a conformational state of the thin filament that suppresses myosin activity. J Biol Chem. 2002;277:27636-27642. (Pubitemid 34966706)
75. Harada K, Potter JD. Familial hypertrophic cardiomyopathy mutations from different functional regions of troponin T result in different effects on the pH and Ca2 + sensitivity of cardiac muscle contraction. J Biol Chem. 2004;279:14488-14495. (Pubitemid 38618835)
76. Chandra M, Tschirgi ML, Tardiff JC. Increase in tension-dependent atp consumption induced by cardiac troponin T mutation. Am J Physiol Heart Circ Physiol. 2005;289:H2112-H2119. (Pubitemid 41507363)
77. Palm T, Graboski S, Hitchcock-DeGregori SE, Greenfield NJ. Disease-causing mutations in cardiac troponin T: identification of a critical tropomyosin-binding region. Biophys J. 2001;81:2827-2837. (Pubitemid 33020068)
78. Hinkle A, Tobacman LS. Folding and function of the troponin tail domain. Effects of cardiomyopathic troponin T mutations. J Biol Chem. 2003;278:506-513. (Pubitemid 36043603)
79. Brooks BR, Bruccolerii RE, Olafson BD, States DJ, Swaminathan S, Karplus M. Charmm: a program for macromolecular energy, minimization, and dynamics calculations. J Comput Chem. 1983;4:187-217.
80. Morimoto S, Lu QW, Harada K, Takahashi-Yanaga F, Minakami R, OhtaM, SasaguriT, Ohtsuki I. Ca(2 + )-desensitizing effect of a deletion mutation delta K210 in cardiac troponin T that causes familial dilated cardiomyopathy. Proc Natl Acad Sci USA. 2002;99:913-918. (Pubitemid 34106610)
81. Lu Q-W, Morimoto S, Harada K, Du C-K, Takahashi-Yanaga F, Miwa Y, Sasaguri T, Ohtsuki I. Cardiac troponin t mutation R141W found in dilated cardiomyopathy stabilizes the troponin T-tropomyosin interaction and causes a Ca2+ desensitization. JMol Cell Cardiol. 2003;35: 1421-1427. (Pubitemid 37491185)
82. Mirza M, Marston S, Willott R, Ashley C, Mogensen J, McKenna W, Robinson P, Redwood C, Watkins H. Dilated cardiomyopathy mutations in three thin filament regulatory proteins result in a common functional phenotype. J Biol Chem. 2005;280:28498-28506. (Pubitemid 41105750)
83. Du CK, Morimoto S, Nishii K, Minakami R, Ohta M, Tadano N, Lu QW, Wang YY, Zhan DY, Mochizuki M, Kita S, Miwa Y, Takahashi-Yanaga F, Iwamoto T, Ohtsuki I, Sasaguri T. Knock-in mouse model of dilated cardiomyopathy caused by troponin mutation. Circ Res. 2007; 101:185-194. (Pubitemid 47196586)
84. Coviello DA, Maron BJ, Spirito P, Watkins H, Vosberg HP, Thierfelder L, Schoen FJ, Seidman JG, Seidman CE. Clinical features of hyper-trophic cardiomyopathy caused by mutation of a "hot spot" in the alpha-tropomyosin gene. J Am Coll Cardiol. 1997;29:635-640. (Pubitemid 27116108)
85. Yamauchi-Takihara K, Nakajima-Taniguchi C, Matsui H, Fujio Y, Kunisada K, Nagata S, Kishimoto T. Clinical implications of hyper-trophic cardiomyopathy associated with mutations in the alpha-tropomyosin gene. Heart. 1996;76:63-65. (Pubitemid 26267141)
86. Nakajima-Taniguchi C, Matsui H, Nagata S, Kishimoto T, Yamauchi-Takihara K. Novel missense mutation in alpha-tropomyosin gene found in Japanese patients with hypertrophic cardiomyopathy. J Mol Cell Cardiol. 1995;27:2053-2058.
87. Karibe A, Tobacman LS, Strand J, Butters C, Back N, Bachinski LL, Arai AE, Ortiz A, Roberts R, Homsher E, Fananapazir L. Hypertrophic cardiomyopathy caused by a novel alpha-tropomyosin mutation (V95A) is associated with mild cardiac phenotype, abnormal calcium binding to troponin, abnormal myosin cycling, and poor prognosis. Circulation. 2001;103:65-71. (Pubitemid 32050437)
88. Mogensen J, Klausen IC, Pedersen AK, Egeblad H, Bross P, Kruse TA, Gregersen N, Hansen PS, Baandrup U, Borglum AD. Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy. J Clin Invest. 1999;103:R39-R43. (Pubitemid 29535504)
89. Arad M, Penas-Lado M, Monserrat L, Maron BJ, Sherrid M, Ho CY, Barr S, Karim A, Olson TM, Kamisago M, Seidman JG, Seidman CE. Gene mutations in apical hypertrophic cardiomyopathy. Circulation. 2005;112:2805-2811. (Pubitemid 41641675)
90. Prabhakar R, Boivin GP, Grupp IL, Hoit B, Arteaga G, Solaro JR, Wieczorek DF. A familial hypertrophic cardiomyopathy alpha-tropomyosin mutation causes severe cardiac hypertrophy and death in mice. J Mol Cell Cardiol. 2001;33:1815-1828. (Pubitemid 32977135)
91. Michele DE, Gomez CA, Hong KE, Westfall MV, Metzger JM. Cardiac dysfunction in hypertrophic cardiomyopathy mutant tropomyosin mice is transgene-dependent, hypertrophy-independent, and improved by beta-blockade. Circ Res. 2002;91:255-262. (Pubitemid 34875681)
92. Olson TM, Kishimoto NY, Whitby FG, Michels VV. Mutations that alter the surface charge of alpha-tropomyosin are associated with dilated cardiomyopathy. J Mol Cell Cardiol. 2001;33:723-732. (Pubitemid 32538985)
93. Olson TM, Michels VV, Thibodeau SN, Tai YS, Keating MT. Actin mutations in dilated cardiomyopathy, a heritable form of heart failure. Science. 1998;280:750-752. (Pubitemid 28243352)
94. Ingwall JS. Transgenesis and cardiac energetics: new insights into cardiac metabolism. J Mol Cell Cardiol. 2004;37:613-623. (Pubitemid 39198936)
95. Song W, Dyer E, Stuckey D, Leung M-C, Memo M, Mansfield C, Ferenczi M, Liu K, Redwood C, Nowak K, Harding S, Clarke K, Wells D, Marston S. Investigation of a transgenic mouse model of familial dilated cardiomyopathy. J Mol Cell Cardiol. 2010;49:380-389.
96. Brown JH, Cohen C. Regulation of muscle contraction by tropomyosin and troponin: how structure illuminates function. Adv Protein Chem. 2005;71:121-159. (Pubitemid 41446928)
97. Brown JH, Kim KH, Jun G, Greenfield NJ, Dominguez R, Volkmann N, Hitchcock-DeGregori SE, Cohen C. Deciphering the design of the tro-pomyosin molecule. Proc Natl Acad Sci USA. 2001;98:8496-8501.
98. Singh A, Hitchcock-DeGregori SE. Local destabilization of the tropo-myosin coiled coil gives the molecular flexibility required for actin binding. Biochemistry. 2003;42:14114-14121. (Pubitemid 37499407)
99. Singh A, Hitchcock-DeGregori SE. Tropomyosin's periods are quasi-equivalent for actin binding but have specific regulatory functions. Biochemistry. 2007;46:14917-14927. (Pubitemid 350308883)
100. Greenfield NJ, Swapna GV, Huang Y, Palm T, Graboski S, Montelione GT, Hitchcock-DeGregori SE. The structure of the carboxyl terminus of striated alpha-tropomyosin in solution reveals an unusual parallel arrangement of interacting alpha-helices. Biochemistry. 2003;42: 614-619. (Pubitemid 36133285)
101. Murakami K, Stewart M, Nozawa K, Tomii K, Kudou N, Igarashi N, Shirakihara Y, Wakatsuki S, Yasunaga T, Wakabayashi T. Structural basis for tropomyosin overlap in thin (actin) filaments and the generation of a molecular swivel by troponin-T. Proc Natl Acad Sci USA. 2008;105:7200-7205. (Pubitemid 351754455)
102. Bottinelli R, Coviello DA, Redwood CS, Pellegrino MA, Maron BJ, Spirito P, Watkins H, Reggiani C. A mutant tropomyosin that causes hypertrophic cardiomyopathy is expressed in vivo and associated with an increased calcium sensitivity. Circ Res. 1998;82:106-115. (Pubitemid 28074023)
103. Michele DE, Albayya FP, Metzger JM. Direct, convergent hypersensitivity of calcium-activated force generation produced by hypertrophic cardiomyopathy mutant alpha-tropomyosins in adult cardiac myocytes. Nat Med. 1999;5:1413-1417.
104. Golitsina N, An Y, Greenfield N, Thierfelder L, Iizuka K, Seidman J, Seidman C, Lehrer S, Hitchcock-DeGregori S. Effects of two familial hypertrophic cardiomyopathy-causing mutations on alpha-tropomyosin structure and function. Biochemistry. 1999;38:3850.
105. Kremneva E, Boussouf S, Nikolaeva O, Maytum R, Geeves MA, Levitsky DI. Effects of two familial hypertrophic cardiomyopathy mutations in alpha-tropomyosin, Asp175Asn and Glu180Gly, on the thermal unfolding of actin-bound tropomyosin. Biophys J. 2004;87: 3922-3933. (Pubitemid 39602898)
106. Muthuchamy M, Pieples K, Rethinasamy P, Hoit B, Grupp IL, Boivin GP, Wolska B, Evans C, Solaro RJ, Wieczorek DF. Mouse model of a familial hypertrophic cardiomyopathy mutation in alpha-tropomyosin manifests cardiac dysfunction. Circ Res. 1999;85:47-56. (Pubitemid 29321041)
107. Heller M, Nili M, Homsher E, Tobacman L. Cardiomyopathic tropomyosin mutations that increase thin filament Ca2+ sensitivity and tropomyosin N-domain flexibility. J Biol Chem. 2003;278:41742-41748. (Pubitemid 37310433)
108. Mirza M, Robinson P, Kremneva E, Copeland On, Nikolaeva O, Watkins H, Levitsky D, Redwood C, El-Mezgueldi M, Marston S. The effect of mutations in alpha-tropomyosin (E40K and E54K) that cause familial dilated cardiomyopathy on the regulatory mechanism of cardiac muscle thin filaments. J Biol Chem. 2007;282:13487-13497. (Pubitemid 47100552)
109. Rajan S, Ahmed RPH, Jagatheesan G, Petrashevskaya N, Boivin GP, Urboniene D, Arteaga GM, Wolska BM, Solaro RJ, Liggett SB, Wieczorek DF. Dilated cardiomyopathy mutant tropomyosin mice develop cardiac dysfunction with significantly decreased fractional shortening and myofilament calcium sensitivity. Circ Res. 2007;101: 205-214. (Pubitemid 47196588)
110. Nirody J, Li X, Sousa D, Sumida J, Fischer S, Lehrer S, Lehman W. Electron microscopy and molecular dynamics on a D137L mutant of tropomyosin. Biophys J. 2010;98(3 Suppl 1):414a. Abstract.
111. Tardiff JC. Sarcomeric proteins and familial hypertrophic cardiomyopathy: linking mutations in structural proteins to complex cardiovascular phenotypes. Heart Fail Rev. 2005;10:237-248. (Pubitemid 43115833)
112. Jagatheesan G, Rajan S, Wieczorek DF. Investigations into tropomyosin function using mouse models. J Mol Cell Cardiol. 2010;48:893-898.
113. Javadpour MM, Tardiff JC, Pinz I, Ingwall JS. Decreased energetics in murine hearts bearing the R92Q mutation in cardiac troponin T. J Clin Invest. 2003;112:768-775. (Pubitemid 38057717)
114. He H, Javadpour MM, Latif F, Tardiff JC, Ingwall JS. R-92L and R-92W mutations in cardiac troponin T lead to distinct energetic phenotypes in intact mouse hearts. Biophys J. 2007;93:1834-1844. (Pubitemid 47403322)
115. Schwartz K, Mercadier J-J. Cardiac troponin T and familial hypertrophic cardiomyopathy: an energetic affair. J Clin Invest. 2003;112:652-654. (Pubitemid 38057704)
116. Crilley JG, Boehm EA, Blair E, Rajagopalan B, Blamire AM, Styles P, McKenna WJ, Ostman-Smith I, Clarke K, Watkins H. Hypertrophic cardiomyopathy due to sarcomeric gene mutations is characterized by impaired energy metabolism irrespective of the degree of hypertrophy. J Am Coll Cardiol. 2003;41:1776-1782. (Pubitemid 36584252)
117. Robinson P, Griffiths P, Watkins H. Dilated and hypertrophic cardiomyopathy mutations in troponin and alpha-tropomyosin have opposing effects on the calcium affinity of cardiac thin filaments. Circ Res. 2007;101:1266-1273. (Pubitemid 350294643)
118. Palmer BM, Fishbaugher DE, Schmitt JP, Wang Y, Alpert NR, Seidman CE, Seidman JG, VanBuren P, Maughan DW. Differential cross-bridge kinetics of FHC myosin mutations R403Q and R453C in heterozygous mouse myocardium. Am J Physiol Heart Circ Physiol. 2004;287: H91-H99. (Pubitemid 38802340)
119. Jagatheesan G, Rajan S, Petrashevskaya N, Schwartz A, Boivin G, Arteaga GM, Solaro RJ, Liggett SB, Wieczorek DF. Rescue of tropomyosin-induced familial hypertrophic cardiomyopathy mice by transgenesis. Am J Physiol Heart Circ Physiol. 2007;293:H949-H958. (Pubitemid 47254193)
120. Baudenbacher F, Schober T, Pinto JR, Sidorov VY, Hilliard F, Solaro RJ, Potter JD, Knollmann BC. Myofilament Ca2+ sensitization causes susceptibility to cardiac arrhythmia in mice. J Clin Invest. 2008;118: 3893-3903.
121. Tikunova SB, Liu B, Swindle N, Little SC, Gomes AV, Swartz DR, Davis JP. Effect of calcium-sensitizing mutations on calcium binding and exchange with troponin C in increasingly complex biochemical systems. Biochemistry. 2010;49:1975-1984.
122. Alves ML, Gaffin RD, Wolska BM. Rescue of familial cardiomyopathies by modifications at the level of sarcomere and Ca2+ fluxes. J Mol Cell Cardiol. 2010;48:834-842.
123. Haim TE, Dowell C, Diamanti T, Scheuer J, Tardiff JC. Independent FHC-related cardiac troponin T mutations exhibit specific alterations in myocellular contractility and calcium kinetics. J Mol Cell Cardiol. 2007;42:1098-1110. (Pubitemid 46829199)
124. Guinto PJ, Haim TE, Dowell-Martino CC, Sibinga N, Tardiff JC. Temporal and mutation-specific alterations in Ca2+ homeostasis differentially determine the progression of cTnT-related cardiomyopathies in murine models. Am J Physiol Heart Circ Physiol. 2009;297: H614-H626.
125. Westermann D, Knollmann BC, Steendijk P, Rutschow S, Riad A, Pauschinger M, Potter JD, Schultheiss H-P, Tschope C. Diltiazem treatment prevents diastolic heart failure in mice with familial hypertrophic cardiomyopathy. Eur J Heart Fail. 2006;8:115-121. (Pubitemid 43240843)
126. Ho CY, Carlsen C, Thune JJ, Havndrup O, Bundgaard H, Farrohi F, Rivero J, Cirino AL, Andersen PS, Christiansen M, Maron BJ, Orav EJ, Køber L. Echocardiographic strain imaging to assess early and late consequences of sarcomere mutations in hypertrophic cardiomyopathy. Circ Cardiovasc Genet. 2009;2:314-321.
127. Predmore JM, Wang P, Davis F, Bartolone S, Westfall MV, Dyke DB, Pagani F, Powell SR, Day SM. Ubiquitin proteasome dysfunction in human hypertrophic and dilated cardiomyopathies. Circulation. 2010; 121:997-1004.
128. Kaski JP, Syrris P, Esteban MTT, Jenkins S, Pantazis A, Deanfield JE, McKenna WJ, Elliott PM. Prevalence of sarcomere protein gene mutations in preadolescent children with hypertrophic cardiomyopathy. Circ Cardiovasc Genet. 2009;2:436-441.
129. Force T, Bonow RO, Houser SR, Solaro RJ, Hershberger RE, Adhikari B, Anderson ME, Boineau R, Byrne BJ, Cappola TP, Kalluri R, LeWinter MM, Maron MS, Molkentin JD, Ommen SR, Regnier M, Tang WH, Tian R, Konstam MA, Maron BJ, Seidman CE. Research priorities in hypertrophic cardiomyopathy: report of a working group of the national heart, lung, and blood institute. Circulation. 2010;122: 1130-1133.