Advertisement

Skeletal Muscle Disease Due to Mutations in Tropomyosin, Troponin and Cofilin

  • Nigel F. Clarke
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 642)

Abstract

Tropomyosin (Tm) and the troponins (troponin I, troponin T and troponin C) are proteins that work cooperatively to regulate muscle contraction, making actin-myosin interactions sensitive to cytosolic calcium levels. Several isoforms exist for each component in this group, each having a specific expression pattern that enables cardiac, slow skeletal (type 1) and fast skeletal (type 2) muscle fibers to have distinct contractile properties. Mutations in all components of this complex have been associated with skeletal muscle disease. The first disease associations were with nemaline myopathy, but recently other congenital myopathies (‘cap disease,’ congenital fiber type disproportion) and other clinical entities (distal arthrogryposis, multiple pterygium syndrome) have been linked to mutations. A homozygous mutation in CFL2, the gene for muscle cofilin, has been associated with nemaline myopathy in one family to date. Researchers have begun to decipher the mechanisms by which these mutations result in muscle weakness and contractures using a variety of in vitro assays to assess the effects of individual mutations on protein function and on sarcomere dynamics.

Keywords

Congenital Myopathy Nemaline Myopathy Familial Hypertrophic Cardiomyopathy Slow Skeletal Muscle Skeletal Muscle Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Perry SV. Vertebrate tropomyosin: distribution, properties and function. J Muscle Res Cell Motil 2001; 22:5–49.PubMedCrossRefGoogle Scholar
  2. 2.
    Schevzov G, Vrhovski B, Bryce NS et al. Tissue-specific tropomyosin isoform composition. J Histochem Cytochem 2005; 53:557–570.PubMedCrossRefGoogle Scholar
  3. 3.
    Gordon AM, Regnier M, Homsher E. Skeletal and cardiac muscle contractile activation: tropomyosin “rocks and rolls”. News Physiol Sci 2001; 16:49–55.PubMedGoogle Scholar
  4. 4.
    Pieples K, Wieczorek DF. Tropomyosin 3 increases striated muscle isoform diversity. Biochemistry 2000; 39:8291–8297.PubMedCrossRefGoogle Scholar
  5. 5.
    Salviati G, Betto R, Danieli BD et al. Myofibrillar-protein isoforms and sarcoplasmic-reticulum Ca2+-transport activity of single human muscle fibers. Biochem J 1984; 224:215–225.PubMedGoogle Scholar
  6. 6.
    Leger J, Bouveret P, Schwartz K et al. A comparative study of skeletal and cardiac tropomyosins: Subunits, thiol group content and biological activities. Pflugers Arch 1976; 362:271–277.PubMedCrossRefGoogle Scholar
  7. 7.
    Bronson DD, Schachat FH. Heterogeneity of contractile proteins. Differences in tropomyosin in fast, mixed and slow skeletal muscles of the rabbit. J Biol Chem 1982; 257:3937–3944.PubMedGoogle Scholar
  8. 8.
    Brown HR, Schachat FH. Renaturation of skeletal muscle tropomyosin: Implications for in vivo assembly. Proc Natl Acad Sci USA 1985; 82:2359–2363.PubMedCrossRefGoogle Scholar
  9. 9.
    Ochala J, Li M, Tajsharghi H et al. Effects of a R133W beta-tropomyosin mutation on regulation of muscle contraction in single human muscle fibers. J Physiol 2007; 581:1283–1292.PubMedCrossRefGoogle Scholar
  10. 10.
    Gordon AM, Homsher E, Regnier M. Regulation of contraction in striated muscle. Physiol Rev 2000; 80:853–924.PubMedGoogle Scholar
  11. 11.
    Thierfelder L, Watkins H, MacRae C et al. Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: A disease of the sarcomere. Cell 1994; 77:701–712.PubMedCrossRefGoogle Scholar
  12. 12.
    Mogensen J, Murphy RT, Shaw T et al. Severe disease expression of cardiac troponin C and T mutations in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol 2004; 44:2033–2040.PubMedCrossRefGoogle Scholar
  13. 13.
    Kimura A, Harada H, Park JE et al. Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy. Nat Genet 1997; 16:379–382.PubMedCrossRefGoogle Scholar
  14. 14.
    Donner K, Ollikainen M, Ridanpaa M et al. Mutations in the beta-tropomyosin (TPM2) gene—A rare cause of nemaline myopathy. Neuromuscul Disord 2002; 12:151–158.PubMedCrossRefGoogle Scholar
  15. 15.
    Ryan MM, Ilkovski B, Strickland CD et al. Clinical course correlates poorly with muscle pathology in nemaline myopathy. Neurology 2003; 60:665–673.PubMedGoogle Scholar
  16. 16.
    Hall JG, Reed SD, Greene G. The distal arthrogryposes: Delineation of new entities—Review and nosologic discussion. Am J Med Genet 1982; 11:185–239.PubMedCrossRefGoogle Scholar
  17. 17.
    Beals RK. The distal arthrogryposes: A new classification of peripheral contractures. Clin Orthop Relat Res 2005; 203–210.Google Scholar
  18. 18.
    Jouk P, Labarre-Vila A, Mezin P et al. A homozygous null mutation in TPM2 gene causes autosomal recessive nemaline myopathy associated with multiple pterygia (Abstract). World Muscle Society 12th International Congress, Sicily, Italy. Neuromusc Disord 2007; 17:837.CrossRefGoogle Scholar
  19. 19.
    Tajsharghi H, Kimber E, Holmgren D et al. Distal arthrogryposis and muscle weakness associated with a beta-tropomyosin mutation. Neutrology 2007; 68:772–775.CrossRefGoogle Scholar
  20. 20.
    Lehtokari VL, Ceuterick-de Groote C, de Jonghe P et al. Cap disease caused by heterozygous deletion of the beta-tropomyosin gene TPM2. Neuromuscul Disord 2007; 17:433–442.PubMedCrossRefGoogle Scholar
  21. 21.
    Tajsharghi H, Ohlsson M, Lindberg C et al. Congenital myopathy with nemaline rods and cap structures caused by a mutation in the beta-tropomyosin gene (TPM2). Arch Neurol 2007; 64:1334–1338.PubMedCrossRefGoogle Scholar
  22. 22.
    Fidzianska A, Badurska B, Ryniewicz B et al. “Cap disease”: New congenital myopathy. Neurology 1981; 31:1113–1120.PubMedGoogle Scholar
  23. 23.
    Bamshad M, Watkins WS, Zenger RK et al. A gene for distal arthrogryposis type I maps to the pericentromeric region of chromosome 9. Am J Hum Genet 1994; 55:1153–1158.PubMedGoogle Scholar
  24. 24.
    Sung SS, Brassington AM, Grannatt K et al. Mutations in genes encoding fast-twitch contractile proteins cause distal arthrogryposis syndromes. Am J Hum Genet 2003; 72:681–690.PubMedCrossRefGoogle Scholar
  25. 25.
    Kohn WD, Kay CM, Hodges RS. Orientation, positional, additivity and oligomerization-state effects of interhelical ion pairs in alpha-helical coiled-coils. J Mol Biol 1998; 283:993–1012.PubMedCrossRefGoogle Scholar
  26. 26.
    Brown JH, Zhou Z, Reshetnikova L et al. Structure of the mid-region of tropomyosin: Bending and binding sites for actin. Proc Natl Acad Sci USA 2005; 102:18878–18883.PubMedCrossRefGoogle Scholar
  27. 27.
    Robinson P, Lipscomb S, Preston LC et al. Mutations in fast skeletal troponin I, troponin T and beta-tropomyosin that cause distal arthrogryposis all increase contractile function. FASEB J 2007; 21:896–905.PubMedCrossRefGoogle Scholar
  28. 28.
    Corbett MA, Akkari PA, Domazetovska A et al. An alphaTropomyosin mutation alters dimer preference in nemaline myopathy. Ann Neurol, 2005; 57:42–49.PubMedCrossRefGoogle Scholar
  29. 29.
    den Dunnen JT, Antonarakis SE. Nomenclature for the description of human sequence variations. Hum Genet 2001; 109:121–124.CrossRefGoogle Scholar
  30. 30.
    Penisson-Besnier I, Monnier N, Toutain A et al. A second pedigree with autosomal dominant nemaline myopathy caused by TPM3 mutation: A clinical and pathological study. Neuromuscul Disord 2007; 17:330–337.PubMedCrossRefGoogle Scholar
  31. 31.
    Araya E, Berthier C, Kim E et al. Regulation of coiled-coil assembly in tropomyosins. J Struct Biol 2002; 137:176–183.PubMedCrossRefGoogle Scholar
  32. 32.
    Dufour C, Weinberger RP, Schevzov G et al. Splicing of two internal and four carboxyl-terminal alternative exons in nonmuscle tropomyosin 5 premRNA is independently regulated during development. J Biol Chem 1998; 273:18547–18555.PubMedCrossRefGoogle Scholar
  33. 33.
    Laing NG, Wilton SD, Akkari PA et al. A mutation in the alpha tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy NEM1. Nat Genet 1995; 9:75–79.PubMedCrossRefGoogle Scholar
  34. 34.
    Clarke NF, Kolski H, Dye DE et al. Mutations in TPM3 are a common cause of congenital fiber type disproportion. Ann Neurol. 2008 Mar:63(3):329–37.PubMedCrossRefGoogle Scholar
  35. 35.
    Clarke NF, Ilkovski B, Cooper S et al. The pathogenesis of ACTA1-related congenital fiber type disproportion. Ann Neurol 2007; 61:552–561.PubMedCrossRefGoogle Scholar
  36. 36.
    Laing NG, Majda BT, Akkari PA et al. Assignment of a gene (NEMI) for autosomal dominant nemaline myopathy to chromosome I. Am J Hum Genet 1992; 50:576–583.PubMedGoogle Scholar
  37. 37.
    Tan P, Briner J, Boltshauser E et al. Homozygosity for a nonsense mutation in the alpha-tropomyosin slow gene TPM3 in a patient with severe infantile nemaline myopathy. Neuromuscul Disord 1999; 9:573–579.PubMedCrossRefGoogle Scholar
  38. 38.
    Durling HJ, Reilich P, Muller-Hocker J et al. De novo missense mutation in a constitutively expressed exon of the slow alpha-tropomyosin gene TPM3 associated with an atypical, sporadic case of nemaline myopathy. Neuromuscul Disord 2002; 12:947–951.PubMedCrossRefGoogle Scholar
  39. 39.
    Wattanasirichaigoon D, Swoboda KJ, Takada F et al. Mutations of the slow muscle alpha-tropomyosin gene, TPM3, are a rare cause of nemaline myopathy. Neurology 2002; 59:613–617.PubMedGoogle Scholar
  40. 40.
    Lehtokari VL, Pelin K, Donner K et al. Identification of a founder mutation in TPM3 in nemaline myopathy patients of Turkish origin. Eur J Hum Genet. 2008 Apr 2; [Epub ahead of print] PMID: 18382475.Google Scholar
  41. 41.
    Wagschal K, Tripet B, Lavigne P et al. The role of position a in determining the stability and oligomerization state of alpha-helical coiled coils: 20 amino acid stability coefficients in the hydrophobic core of proteins. Protein Sci 1999; 8:2312–2329.PubMedCrossRefGoogle Scholar
  42. 42.
    Corbett MA, Robinson CS, Dunglison GF et al. A mutation in alpha-tropomyosin(slow) affects muscle strength, maturation and hypertrophy in a mouse model for nemaline myopathy. Hum Mol Genet 2001; 10:317–328.PubMedCrossRefGoogle Scholar
  43. 43.
    Akkari PA, Song Y, Hitchcock-DeGregori S et al. Expression and biological activity of Baculovirus generated wild-type human slow alpha tropomyosin and the Met9Arg mutant responsible for a dominant form of nemaline myopathy. Biochem Biophys Res Commun 2002; 296:300–304.PubMedCrossRefGoogle Scholar
  44. 44.
    Moraczewska J, Greenfield NJ, Liu Y et al. Alteration of tropomyosin function and folding by a nemaline myopathy-causing mutation. Biophys J 2000; 79:3217–3225.PubMedCrossRefGoogle Scholar
  45. 45.
    Greenfield NJ, Fowler VM. Tropomyosin requires an intact N-terminal coiled coil to interact with tropomodulin. Biophys J 2002; 82:2580–2591.PubMedCrossRefGoogle Scholar
  46. 46.
    de Haan A, van der Vliet MR, Gommans IM et al. Skeletal muscle of mice with a mutation in slow alpha-tropomyosin is weaker at lower lengths. Neuromuscul Disord 2002; 12:952–957.PubMedCrossRefGoogle Scholar
  47. 47.
    Michele DE, Albayya FP, Metzger JM. A nemaline myopathy mutation in alpha-tropomyosin causes defective regulation of striated muscle force production. J Clin Invest 1999; 104:1575–1581.PubMedCrossRefGoogle Scholar
  48. 48.
    Johnston JJ, Kelley RI, Crawford TO et al. A novel nemaline myopathy in the Amish caused by a mutation in troponin T1. Am J Hum Genet 2000; 67:814–821.PubMedCrossRefGoogle Scholar
  49. 49.
    Jin JP, Brotto MA, Hossain MM et al. Truncation by Glu180 nonsense mutation results in complete loss of slow skeletal muscle troponin T in a lethal nemaline myopathy. J Biol Chem 2003; 278:26159–26165.PubMedCrossRefGoogle Scholar
  50. 50.
    Wang X, Huang QQ, Breckenridge MT et al. Cellular fate of truncated slow skeletal muscle troponin T produced by Glu180 nonsense mutation in amish nemaline myopathy. J Biol Chem 2005; 280:13241–13249.PubMedCrossRefGoogle Scholar
  51. 51.
    Sung SS, Brassington AM, Krakowiak PA et al. Mutations in TNNT3 Cause Multiple Congenital Contractures: A Second Locus for Distal Arthrogryposis Type 2B. Am J Hum Genet 2003; 73:212–214.PubMedCrossRefGoogle Scholar
  52. 52.
    Varnava A, Baboonian C, Davison F et al. A new mutation of the cardiac troponin T gene causing familial hypertrophic cardiomyopathy without left ventricular hypertrophy. Heart 1999; 82:621–624.PubMedGoogle Scholar
  53. 53.
    Krakowiak PA, O’Quinn JR, Bohnsack JF et al. A variant of Freeman-Sheldon syndrome maps to 11p15.5-pter. Am J Hum Genet 1997; 60:426–432.PubMedGoogle Scholar
  54. 54.
    Drera B, Zoppi N, Barlati S et al. Recurrence of the p.R156X TNN12 mutation in distal arthrogryposis type 2B. Clin Genet 2006; 70:532–534.PubMedCrossRefGoogle Scholar
  55. 55.
    Jiang M, Zhao X, Han W et al. A novel deletion in TNN12 causes distal arthrogryposis in a large Chinese family with marked variability of expression. Hum Genet 2006; 120:238–242.PubMedCrossRefGoogle Scholar
  56. 56.
    Kimber E, Tajsharghi H, Kroksmark AK et al. A mutation in the fast skeletal muscle troponin 1 gene causes myopathy and distal arthrogryposis. Neurology 2006; 67:597–601.PubMedCrossRefGoogle Scholar
  57. 57.
    Shrimpton AE, Hoo JJ. A TNN12 mutation in a family with distal arthrogryposis type 2B. Eur J Med Genet 2006; 49:201–206.PubMedCrossRefGoogle Scholar
  58. 58.
    Toydemir RM, Rutherford A, Whitby FG et al. Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome. Nat Genet 2006; 38:561–565.PubMedCrossRefGoogle Scholar
  59. 59.
    Ramos CH. Mapping subdomains in the C-terminal region of troponin I involved in its binding to troponin C and to thin filament. J Biol Chem 1999; 274:18189–18195.PubMedCrossRefGoogle Scholar
  60. 60.
    Thirion C, Stucka R, Mendel B et al. Characterization of human muscle type cofilin (CFL2) in normal and regenerating muscle. Eur J Biochem 2001; 268:3473–3482.PubMedCrossRefGoogle Scholar
  61. 61.
    Agrawal PB, Greenleaf RS, Tomczak KK et al. Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2. Am J Hum Genet 2007; 80:162–167.PubMedCrossRefGoogle Scholar
  62. 62.
    Oldfors A. Hereditary myosin myopathies. Neuromuscul Disord 2007; 17:355–367.PubMedCrossRefGoogle Scholar
  63. 63.
    Geisterfer-Lowrance AA, Kass S, Tanigawa G et al. A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell 1990; 62:999–1006.PubMedCrossRefGoogle Scholar
  64. 64.
    Meredith C, Herrmann R, Parry C et al. Mutations in the slow skeletal muscle fiber myosin heavy chain gene (MYH7) cause laing early-onset distal myopathy (MPD1). Am J Hum Genet 2004; 75:703–708.PubMedCrossRefGoogle Scholar
  65. 65.
    Vrhovski B, Lemckert F, Gunning P. Modification of the tropomyosin isoform composition of actin filaments in the brain by deletion of an alternatively spliced exon. Neuropharmacology 2004; 47:684–693.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2008

Authors and Affiliations

  • Nigel F. Clarke
    • 1
  1. 1.Institute for Neuromuscular Research, Children’s Hospital at Westmead, Discipline of Pediatrics and Child HealthUniversity of SydneySydneyAustralia

Personalised recommendations