Tropomyosin pp 201-222 | Cite as

Human Tropomyosin Isoforms in the Regulation of Cytoskeleton Functions

  • Jim Jung-Ching LinEmail author
  • Robbin D. Eppinga
  • Kerri S. Warren
  • Keith R. McCrae
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 644)


Over the past two decades, extensive molecular studies have identified multiple tropomyosin isoforms existing in all mammalian cells and tissues. In humans, tropomyosins are encoded by TPM1 (α-Tm, 15q22.1), TPM2 (β-Tm, 9p13.2–p13.1), TPM3 (γ-Tm, 1q21.2) and TPM4 (δ-Tm, 19p13.1) genes. Through the use of different promoters, alternatively spliced exons and different sites of poly(A) addition signals, at least 22 different tropomyosin cDNAs with full-length open reading frame have been cloned. Compelling evidence suggests that these isoforms play important determinants for actin cytoskeleton functions, such as intracellular vesicle movement, cell migration, cytokinesis, cell proliferation and apoptosis. In vitro biochemical studies and in vivo localization studies suggest that different tropomyosin isoforms have differences in their actin-binding properties and their effects on other actin-binding protein functions and thus, in their specification of actin microfilaments. In this chapter, we will review what has been learned from experimental studies on human tropomyosin isoforms about the mechanisms for differential localization and functions of tropomyosin. First, we summarize current information concerning human tropomyosin isoforms and relate this to the functions of structural homologues in rodents. We will discuss general strategies for differential localization of tropomyosin isoforms, particularly focusing on differential protein turnover and differential isoform effects on other actin binding protein functions. We will then review tropomyosin functions in regulating cell motility and in modulating the anti-angiogenic activity of cleaved high molecular weight kininogen (HKa) and discuss future directions in this area.


Actin Dynamic Nemaline Myopathy High Molecular Weight Kininogen Nonmuscle Cell Myosin ATPase Activity 
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.


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  1. 1.
    Cooper JA. Actin dynamics: tropomyosin provides stability. Curr Biol 2002; 12:R523–R525.PubMedCrossRefGoogle Scholar
  2. 2.
    Gunning P, Hardeman E, Jeffrey P et al. Creating intracellular structural domains: spatial segregation of actin and tropomyosin isoforms in neurons. Bioessays 1998; 20:892–900.PubMedCrossRefGoogle Scholar
  3. 3.
    Gunning P, O’Neill G, Hardeman E. Tropomyosin-based regulation of the actin cytoskeleton in time and space. Physiol Rev 2008; 88(1):1–35.PubMedCrossRefGoogle Scholar
  4. 4.
    Gunning P, Weinberger R, Jeffrey P et al. Isoform sorting and the creation of intracellular compartments. Annu Rev Cell Dev Biol 1998; 14:339–372.PubMedCrossRefGoogle Scholar
  5. 5.
    Gunning PW, Schevzov G, Kee AJ et al. Tropomyosin isoforms: divining rods for actin cytoskeleton function. Trends Cell Biol 2005; 15:333–341.PubMedCrossRefGoogle Scholar
  6. 6.
    Perry SV. Vertebrate tropomyosin: distribution, properties and function. J Muscle Res Cell Motil 2001; 22:5–49.PubMedCrossRefGoogle Scholar
  7. 7.
    Pittenger MF, Kazzaz JA, Helfman DM. Functional properties of nonmuscle tropomyosin isoforms. Curr Opin Cell Biol 1994; 6:96–104.PubMedCrossRefGoogle Scholar
  8. 8.
    Lin JJ, Warren KS, Wamboldt DD et al. Tropomyosin isoforms in nonmuscle cells. Int Rev Cytol 1997; 170:1–38.PubMedCrossRefGoogle Scholar
  9. 9.
    Lees-Miller JP, Helfman DM. The molecular basis for tropomyosin isoform diversity. Bio Essays 1991; 13:429–437.Google Scholar
  10. 10.
    Lees-Miller JP, Goodwin LO, Helfman DM. Three novel brain tropomyosin isoforms are expressed from the rat α-tropomyosin gene through the use of alternative promoters and alternative RNA processing. Mol Cell Biol 1990; 10:1729–1742.PubMedGoogle Scholar
  11. 11.
    Dufour C, Weinberger RP, Schevzov G et al. Splicing of two internal and four carboxyl-terminal alternative exons in nonmuscle tropomyosin 5 prem RNA is independently regulated during development. J Biol Chem 1998; 273:18547–18555.PubMedCrossRefGoogle Scholar
  12. 12.
    Goodwin LO, Lees-Miller JP, Leonard MA et al. Four fibroblast tropomyosin isoforms are expressed from the rat a-tropomyosin gene via alternative RNA splicing and the use of two promoters. J Biol Chem 1991; 266:8408–8415.PubMedGoogle Scholar
  13. 13.
    Wieczorek DF, W.Sc, Nadal-Ginard B. The rat alpha-tropomyosin gene generates a minimum of six different mRNAs coding for striated, smooth and nonmuscle isoforms by alternative splicing. Mol Cell Biol 1988; 8:679–694.PubMedGoogle Scholar
  14. 14.
    Marston SB, Redwood CS. Modulation of thin filament activation by breakdown or isoform switching of thin filament proteins. Circ Res 2003; 93:1170–1178.PubMedCrossRefGoogle Scholar
  15. 15.
    Reinach FC, Macleod AR. Tissue-specific expression of the human tropomyosin gene involved in the generation of the trk oncogene. Nature 1986; 322:648–650.PubMedCrossRefGoogle Scholar
  16. 16.
    Novy RE, Lin JL-C, Lin CS et al. Human fibroblast tropomyosin isoforms: characterization of cDNA clones and analysis of tropomyosin isoform expression in human tissues and in normal and transformed cells. Cell Motil Cytoskeleton 1993; 25:267–281.PubMedCrossRefGoogle Scholar
  17. 17.
    Pieples K, Wieczorek DF. Tropomyosin 3 increases striated muscle isoform diversity. Biochemistry 2000; 39:8291–8297.PubMedCrossRefGoogle Scholar
  18. 18.
    Lin CS, Leavitt J. Cloning and characterization of a cDNA encoding transforming-senstive tropomyosin isoform 3 from tumorigenic human fibroblasts. Mol Cell Biol 1988; 8:160–168.PubMedGoogle Scholar
  19. 19.
    MacLeod AR, Gooding C. Human hTMα gene: Expression in muscle and nonmuscle tissue. Mol Cell Biol 1988; 8:433–440.PubMedGoogle Scholar
  20. 20.
    MacLeod AR, Houlker C, Reinach FC et al. A muscle-type tropomyosin in human fibroblasts: Evidence for expression by an alternative RNA splicing mechanism. Proc Natl Acad Sci USA 1985; 82:7835–7839.PubMedCrossRefGoogle Scholar
  21. 21.
    MacLeod AR, Houlker C, Reinach FC et al. The mRNA and RNA copy pseudogenes encoding TM30nm, a human cytoskeletal tropomyosin. Nucleic Acids Res 1986; 14:8413–8426.PubMedCrossRefGoogle Scholar
  22. 22.
    MacLeod AR, Talbot K, Smilie LB et al. Characterization of a cDNA defining a gene family encoding TM30pl, a human fibroblast tropomyosin. J Mol Biol 1987; 194:1–10.PubMedCrossRefGoogle Scholar
  23. 23.
    Kee AJ, Schevzov G, Nair-Shalliker V et al. Sorting of a nonmuscle tropomyosin to a novel cytoskeletal compartment in skeletal muscle results in muscular dystrophy. J Cell Biol 2004; 166:685–696.PubMedCrossRefGoogle Scholar
  24. 24.
    Izumo S, Nadal-Ginard B, Mahdavi V. Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload. Proc Natl Acad Sci USA 1988; 85:339–343.PubMedCrossRefGoogle Scholar
  25. 25.
    Muthuchamy M, Pajak L, Howles P et al. Developmental analysis of tropomyosin gene expression in embryonic stem cells and mouse embryos. Mol Cell Biol 1993; 13:3311–3323.PubMedGoogle Scholar
  26. 26.
    L’Ecuyer TJ, Schulte D, Lin JJ-C. Thin filament changes during in vivo rat heart development. Pediatr Res 1991; 30:232–238.PubMedGoogle Scholar
  27. 27.
    Wang S-M, Wang S-H, Lin JL-C et al. Striated muscle tropomyosin-enriched microfiliaments of developing muscles of chicken embryos. J Muscle Res Cell Motil 1990; 11:191–202.PubMedCrossRefGoogle Scholar
  28. 28.
    Sung LA, Gao K-M, Yee LJ et al. Tropomyosin isoform 5b is expressed in human erythrocytes: implications of tropomodulin-TM5 or tropomodulin-TM5b complexes in the protofilament and hexagonal organization of membrane skeletons. Blood 2000; 95:1473–1480.PubMedGoogle Scholar
  29. 29.
    Sung LA, Lin JJ-C. Erythrocyte tropomodulin binds to the N-terminaus of hTM5, a tropomyosin isoform encoded by the γ-tropomyosin gene. Biochem Biophys Res Commun 1994; 201:627–634.PubMedCrossRefGoogle Scholar
  30. 30.
    Vera C, Sood A, Gao KM et al. Tropomodulin-binding site mapped to residues 7–14 at the N-terminal heptad repeats of tropomyosin isoform 5. Arch Biochem Biophys 2000; 378:16–24.PubMedCrossRefGoogle Scholar
  31. 31.
    Mohandas N, Evans E. Mechanical properties of the red cell membrane in relation to molecular structure and genetic defects. Annu Rev Biophys Biomol Struct 1994; 23:787–818.PubMedCrossRefGoogle Scholar
  32. 32.
    An X, Salomao M, Guo X et al. Tropomyosin modulates erythrocyte membrane stability. Blood 2007; 109:1284–1288.PubMedCrossRefGoogle Scholar
  33. 33.
    Lin JL, Geng X, Bhattacharya SD et al. Isolation and sequencing of a novel tropomyosin isoform preferentially associated with colon cancer. Gastroenterology 2002; 123:152–162.PubMedCrossRefGoogle Scholar
  34. 34.
    Pollard TD, Blanchoin L, Mullins RD. Molecular mechanisms controlling actin filament dynamics in nonmuscle cells. Annu Rev Biophys Biomol Struct 2000; 29:545–576.PubMedCrossRefGoogle Scholar
  35. 35.
    Theriot JA, Mitchison TJ. Actin microfilament dynamics in locomoting cells. Nature 1991; 352:126–131.PubMedCrossRefGoogle Scholar
  36. 36.
    Carthew RW. Adhesion proteins and the control of cell shape. Curr Opin Genet Dev 2005; 15:358–363.PubMedCrossRefGoogle Scholar
  37. 37.
    Smythe E, Ayscough KR. Actin regulation in endocytosis. J Cell Sci 2006; 119:4589–4598.PubMedCrossRefGoogle Scholar
  38. 38.
    Pollard TD, Borisy GG. Cellular motility driven by assembly and disassembly of actin filaments. Cell 2003; 112:453–465.PubMedCrossRefGoogle Scholar
  39. 39.
    Houle F, Rousseau S, Morrice N et al. Extracellular signal-regulated kinase mediates phosphorylation of tropomyosin-1 to promote cytoskeleton remodeling in response to oxidative stress: Impact on membrane blebbing. Mol Biol Cell 2003; 14:1418–1432.PubMedCrossRefGoogle Scholar
  40. 40.
    Prasad SVN, Jayatilleke A, Madamanchi A et al. Protein kinase activity of phosphoinositide 3-kinase regulates β-adrenergic receptor endocytosis. Nat Cell Biol 2005; 7:785–796.CrossRefGoogle Scholar
  41. 41.
    Matsumura F, Yamashiro-Matsumura S. Purification and characterization of multiple isoforms of tropomyosin from rat cultured cells. J Biol Chem 1985; 260:13851–13859.PubMedGoogle Scholar
  42. 42.
    Lin JJ, Helfman DM, Hughes SH et al. Tropomyosin isoforms in chicken embryo fibroblasts: purification, characterization and changes in Rous sarcoma virus-transformed cells. J Cell Biol 1985; 100:692–703.PubMedCrossRefGoogle Scholar
  43. 43.
    Lin JJ-C, Hegmann TE, Lin JL. Differential localization of tropomyosin isoforms in cultured nonmuscle cells. J Cell Biol 1988; 107:563–572.PubMedCrossRefGoogle Scholar
  44. 44.
    Vibert P, Craig R, Lehman W. Steric-model for activation of muscle thin filaments. J Mol Biol 1997; 266:8–14.PubMedCrossRefGoogle Scholar
  45. 45.
    Kress M, Huxley HE, Faruqi AR et al. Structural changes during activation of frog muscle studied by time-resolved X-ray diffraction. J Mol Biol 1986; 188:325–342.PubMedCrossRefGoogle Scholar
  46. 46.
    McKillop DF, Geeves MA. Regulation of the interaction between actin and myosin subfragment 1: evidence for three states of the filament. Biophys J 1993; 65:693–701.PubMedCrossRefGoogle Scholar
  47. 47.
    Lehman W, Hatch V, Korman V et al. Tropomyosin and actin isoforms modulate the localization of tropomyosin strands on actin filaments. J Mol Biol 2000; 302:593–606.PubMedCrossRefGoogle Scholar
  48. 48.
    Pieples K, Arteaga G, Solaro RJ et al. Tropomyosin 3 expression leads to hypercontractility and attenuates myofilament length-dependent Ca2+ activation. Am J Physiol Heart Circ Physiol 2002; 283: H1344–H1353.PubMedGoogle Scholar
  49. 49.
    Muthuchamy M, Grupp I, Grupp G et al. Molecular and physiological effects of overexpressing striated muscle β-tropomyosin in the adult murine heart. J Biol Chem 1995; 270:30593–30603.PubMedCrossRefGoogle Scholar
  50. 50.
    Ochala J, Li M, Tajsharghi H et al. Effects of a R133W β-tropomyosin mutation on regulation of muscle contraction in single human muscle fibers. J Physiol 2007; 581:1283–1292.PubMedCrossRefGoogle Scholar
  51. 51.
    Bos JM, Ommen SR, Ackerman MJ. Genetics of hypertrophic cardiomyopathy: one, two, or more diseases? Curr Opin Cardiol 2007; 22:193–199.PubMedCrossRefGoogle Scholar
  52. 52.
    Golitsina N, An Y, Greenfield NJ et al. Effects of two familial hypertrophic cardiomyopathy-causing mutations on α-tropomyosin structure and function. Biochemistry 1997; 36:4637–4642.PubMedCrossRefGoogle Scholar
  53. 53.
    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
  54. 54.
    Boussouf SE, Maytum R, Jaquet K et al. Role of tropomyosin isoforms in the calcium senstivity of striated muscle thin filaments. J Muscle Res Cell Motil 2007; 28:49–58.PubMedCrossRefGoogle Scholar
  55. 55.
    Laing NG, Wilton SD, Akkari PA et al. A mutation in the α tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy. Nat Gent 1995; 9:75–79.CrossRefGoogle Scholar
  56. 56.
    Tajsharghi H, Kimber E, Holmgren D et al. Distal arthrogryposis and muscle weakness associated with a β-tropomyosin mutation. Neurology 2007; 68:772–775.PubMedCrossRefGoogle Scholar
  57. 57.
    Palmiter KA, kitada Y, Muthuchamy M et al. Exchange of β-for α-tropomyosin in hearts of transgenic mice induces change in thin filament response to Ca2+ strong cross-bridge binding and protein phophorylation. J Biol Chem 1996; 271:11611–11614.PubMedCrossRefGoogle Scholar
  58. 58.
    Graceffa P. Phosphorylation of smooth muscle myosin heads regulates the head-induced movement of tropomyosin. J Biol Chem 2000; 275:17143–17148.PubMedCrossRefGoogle Scholar
  59. 59.
    Graceffa P. Movement of smooth muscle tropomyosin by myosin heads. Biochemistry 1999; 38:11984–11992.PubMedCrossRefGoogle Scholar
  60. 60.
    Graceffa P, Mazurkie A. Effect of caldesmon on the position and myosin-induced movement of smooth muscle tropomyosin bound to actin. J Biol Chem 2005; 280:4135–4143.PubMedCrossRefGoogle Scholar
  61. 61.
    Sobue K, Sellers JR. Caldesmon, a novel regulatory protein in smooth muscle and nonmuscle actomyosin systems. J Biol Chem 1991; 266:12115–12118.PubMedGoogle Scholar
  62. 62.
    Smith CW, Pritchard K, Marston SB. The mechanism of Ca2+ regulation of vascular smooth muscle thin filaments by caldesmon and calmodulin. J Biol Chem 1987; 262:116–122.PubMedGoogle Scholar
  63. 63.
    Chalovich JM, Cornelius P, Benson CE. Caldesmon inhibits skeletal actomyosin subfragment-1 ATPase activity and the binding of myosin subfragment-1 to actin. J Biol Chem 1987; 262:5711–5716.PubMedGoogle Scholar
  64. 64.
    Marston S. Aorta caldesmon inhibits actin activation of thiophosphorylated heavy meromyosin Mg2+-ATPase activity by slowing the rate of product release. FEBS Lett 1988; 238:147–150.PubMedCrossRefGoogle Scholar
  65. 65.
    Horiuchi KY, Samuel M, Chacko S. Mechanism for the inhibition of acto-heavy meromyosin ATPase by the actin/calmodulin binding domain of caldesmon. Biochemistry 1991; 30:712–717.PubMedCrossRefGoogle Scholar
  66. 66.
    Yamashiro-Matsumura S, Matsumura F. Characterization of 83-kilodalton nonmuscle caldesmon from cultured rat cells: stimulation of actin binding of nonmuscle tropomyosin and periodic localization along microfilaments like tropomyosin. J Cell Biol 1988; 106:1973–1983.PubMedCrossRefGoogle Scholar
  67. 67.
    Novy RE, Sellers JR, Liu LF et al. In vitro functional characterization of bacterially expressed human fibroblast tropomyosin isoforms and their chimeric mutants. Cell Motil Cytoskeleton 1993; 26:248–261.PubMedCrossRefGoogle Scholar
  68. 68.
    Pittenger MF, Kistler A, Helfman DM. Alternatively spliced exons of the βTM gene exhibit different affinities for F-actin and effects with nonmuscle caldesmon. J Cell Sci 1995; 108:3253–3265.PubMedGoogle Scholar
  69. 69.
    Warren KS, Lin JL, Wamboldt DD et al. Overexpression of human fibroblast caldesmon fragment containing actin-, Ca++/calmodulin-and tropomyosin-binding domains stabilizes endogenous tropomyosin and microfilaments. J Cell Biol 1994; 125:359–368.PubMedCrossRefGoogle Scholar
  70. 70.
    Nosaka S, Onji T, Shibata N. Enhancement of actomyosin ATPase activity by tropomyosin. Recombination of myosin and tropomyosin between muscles and platelet. Biochim Biophys Acta 1984; 788:290–297.PubMedGoogle Scholar
  71. 71.
    Sobieszek A, Small JV. Regulation of the actin-myosin interaction in vertebrate smooth muscle: activation via a myosin light-chain kinase and the effect of tropomyosin. J Mol Biol 1977; 112:559–576.PubMedCrossRefGoogle Scholar
  72. 72.
    Sobieszek A, Small JV. Effect of muscle and nonmuscle tropomyosins in reconstituted skeletal muscle actomyosin. Eur J Biochem 1981; 118:533–539.PubMedCrossRefGoogle Scholar
  73. 73.
    Sobieszek A. Steady-state kinetic studies on the actin activation of skeletal muscle heavy meromyosin subfragments. Effects of skeletal, smooth and nonmuscle tropomyosins. J Mol Biol 1982; 157:275–286.PubMedCrossRefGoogle Scholar
  74. 74.
    Lehrer SS, Morris EP. Dual effects of tropomyosin and troponin-tropomyosin on actomyosin subfragment 1 ATPase. J Biol Chem 1982; 257:8073–8080.PubMedGoogle Scholar
  75. 75.
    Eaton BL, Kominz DR, Eisenberg E. Correlation between the inhibition of the acto-heavy meromyosin ATPase and the binding of tropomyosin to F-actin: Effects of Mg++, KCl, troponin I and Troponin C. Biochemistry 1975; 14:2718–2724.PubMedCrossRefGoogle Scholar
  76. 76.
    Fanning AS, Wolenski JS, Mooseker MS et al. Differential regulation of skeletal muscle myosin-II and brush border myosin-I enzymology and mechanochemistry by bacterially produced tropomyosin isoforms. Cell Motil Cytoskeleton 1994; 29:29–45.PubMedCrossRefGoogle Scholar
  77. 77.
    Pittenger MF, Helfman DM. In vitro and in vivo characterization of four fibroblast tropomyosins produced in bacteria: TM-2, TM-3, TM-5a and TM-5b are colocalized in interphase fibroblasts. J Cell Biol 1992; 118:841–858.PubMedCrossRefGoogle Scholar
  78. 78.
    Moraczewska J, Nickolson-Flynn K, Hitchcock-DeGregori SE. The ends of tropomyosin are major determinants of actin affinity and myosin subfragment 1-induced binding to F-actin in the open state. Biochemistry 1999; 38:15885–15892.PubMedCrossRefGoogle Scholar
  79. 79.
    Jancso A, Graceffa P. Smooth muscle tropomyosin coiled-coil dimers: subunit composition, assembly and end-to-end interaction. J Biol Chem 1991; 266:5891–5897.PubMedGoogle Scholar
  80. 80.
    Sanders C, Burtnick LD, Smillie LB. Native chicken gizzard tropomyosin is predominantly a beta gamma-heterodimer. J Biol Chem 1986; 261:12774–12778.PubMedGoogle Scholar
  81. 81.
    Gimona M, Watakabe A, Helfman DM. Specificity of dimer formation in tropomyosins: influence of alternatively spliced exons on homodimer and heterodimer assembly. Proc Natl Acad Sci USA 1995; 92:9776–9780.PubMedCrossRefGoogle Scholar
  82. 82.
    Prasad GL, Fuldner RA, Braverman R et al. Expression, cytoskeletal utilization and dimer formation of tropomyosin derived from retroviral-mediated cDNA transfer. Metabolism of tropomyosin from transduced cDNA. Eur J Biochem 1994; 224:1–10.PubMedCrossRefGoogle Scholar
  83. 83.
    DesMarais V, Ichetovkin I, Condeelis J et al. Spatial regulation of actin dynamics: a tropomyosin-free, actin-rich compartment at the leading edge. J Cell Sci 2002; 115:4649–4660.PubMedCrossRefGoogle Scholar
  84. 84.
    Blanchoin L, Pollard TD, Hitchcock-DeGregori SE. Inhibition of the Arp2/3 complex-nucleated actin polymerization and branch formation by tropomyosin. Curr Biol 2001; 11:1300–1304.PubMedCrossRefGoogle Scholar
  85. 85.
    Wawro B, Greenfield NJ, Wear MA et al. Tropomyosin regulates elongation by formin at the fast-growing end of the actin filament. Biochemistry 2007; 46:8146–8155.PubMedCrossRefGoogle Scholar
  86. 86.
    Bernstein BW, Bamburg JR. Tropomyosin binding to F-actin protects the F-actin from disassembly by brain actin-depolymerizing factor (ADF). Cell Motil 1982; 2:1–8.PubMedCrossRefGoogle Scholar
  87. 87.
    Ono S, Ono K. Tropomyosin inhibits ADF/cofilin-dependent actin filament dynamics. J Cell Biol 2002; 156:1065–1076.PubMedCrossRefGoogle Scholar
  88. 88.
    Nishida E, Muneyuki E, Maekawa S et al. An actin-depolymerizing protein (destrin) from porcine kidney. Its action on F-actin containing or lacking tropomyosin. Biochemistry 1985; 24:6624–6630.PubMedCrossRefGoogle Scholar
  89. 89.
    Hitchcock SE, Carisson L, Lindberg U. Depolymerization of F-actin by deoxyribonuclease I. Cell 1976; 7:531–542.PubMedCrossRefGoogle Scholar
  90. 90.
    Ishikawa R, Yamashiro S, Matsumura F. Annealing of gelsolin-severed actin fragments by tropomyosin in the presence of Ca2+. Potentiation of the annealing process by caldesmon. J Biol Chem 1989; 264:16764–16770.PubMedGoogle Scholar
  91. 91.
    Fattoum A, Hartwig JH, Stossel TP. Isolation and some structural and functional properties of macrophage tropomyosin. Biochemistry 1983; 22:1187–1193.PubMedCrossRefGoogle Scholar
  92. 92.
    Nyakern-Meazza M, Narayan K, Schutt CE et al. Tropomyosin and gelsolin cooperate in controlling the microfilament system. J Biol Chem 2002; 277:28774–28779.PubMedCrossRefGoogle Scholar
  93. 93.
    Burgess DR, Broschat KO, Hayden JM. Tropomyosin distinguishes between the two actin-binding sites of villin and affects actin-binding properties of other brush border proteins. J Cell Biol 1987; 104:29–40.PubMedCrossRefGoogle Scholar
  94. 94.
    Kobayashi R, Nonomura Y, Okano A et al. Purification and some of the properties of porcine kidney tropomyosin. J Biochem (Tokyo) 1983; 94:171–179.Google Scholar
  95. 95.
    Fischer RS, Fowler VM. Tropomodulins: life at the slow end. Trends Cell Biol 2003; 13:593–601.PubMedCrossRefGoogle Scholar
  96. 96.
    Broschat KO, Weber A, Burgess DR. Tropomyosin stablizes the pointed end of actin filaments by slowing depolymerization. Biochemistry 1989; 28:8501–8506.PubMedCrossRefGoogle Scholar
  97. 97.
    Matsumura F, Yamashiro-Matsumura S. Modulation of actin-bundling activity of 55-kDa protein by multiple isoforms of tropomyosin. J Biol Chem 1986; 261:4655–4659.PubMedGoogle Scholar
  98. 98.
    Bryan J, Edwards R, Matsudaira P et al. Fascin, an echinoid actin-bundling protein, is a homolog of the Drosophila singed gene product. Proc Natl Acad Sci USA 1993; 90:9115–9119.PubMedCrossRefGoogle Scholar
  99. 99.
    Bryce NS, Schevzov G, Ferguson V et al. Specification of actin filament function and molecular composition by tropomyosin isoforms. Mol Biol Cell 2003; 14:1002–1016.PubMedCrossRefGoogle Scholar
  100. 100.
    Schevzov G, Vrhovski B, Bryce NS et al. Tissue-specific tropomyosin isoform composition. J Histochem Cytochem 2005; 53:557–570.PubMedCrossRefGoogle Scholar
  101. 101.
    Hillberg L, Zhao Rathje LS, Nyakern-Meazza M et al. Tropomyosins are present in lamellipodia of motile cells. Eur J Cell Biol 2006; 85:399–409.PubMedCrossRefGoogle Scholar
  102. 102.
    Gupton SL, Anderson KL, Kole TP et al. Cell migration without a lamellipodium: translation of actin dynamics into cell movement mediated by tropomyosin. J Cell Biol 2005; 168:619–631.PubMedCrossRefGoogle Scholar
  103. 103.
    Temm-Grove CJ, Guo W, Helfman DM. Low molecular weight rat fibroblast tropomyosin 5 (TM5): cDNA cloning, actin-binding, localization and coiled-coil interactions. Cell Motil Cytoskel 1996; 33:223–240.CrossRefGoogle Scholar
  104. 104.
    Iwasa JH, Mullins RD. Spatial and temporal relationships between actin-filament nucleation, capping and disassembly. Curr Biol 2007; 17:395–406.PubMedCrossRefGoogle Scholar
  105. 105.
    Prasad GL. Regulation of the expression of tropomyosins and actin cytoskeleton by ras transformation. Meth Enzymol 2005; 407:410–422.CrossRefGoogle Scholar
  106. 106.
    Prasad GL, Fuldner RA, Cooper HL. Expression of transduced tropomyosin 1 cDNA suppresses neoplastic growth of cells transformed by the ras on cogene. Proc Natl Acad Sci USA 1993; 90:7039–7043.PubMedCrossRefGoogle Scholar
  107. 107.
    Prasad GL, Masuelli L, Raj MH et al. Suppression of src-induced transformed phenotype by expression of tropomyosin-1. Oncogene 1999; 18:2027–2031.PubMedCrossRefGoogle Scholar
  108. 108.
    Bakin AV, Safina A, Rinehart C et al. A critical role of tropomyosins in TGF-β regulation of the actin cytoskeleton and cell motility in epithelial cells. Mol Biol Cell 2004; 15:4682–4694.PubMedCrossRefGoogle Scholar
  109. 109.
    Varga AE, Storman NV, Zheng Q et al. Silencing of the tropomyosin-1 gene by DNA methylation alters tumor suppressor function of TGF-β. Oncogene 2005; 24:5043–5052.PubMedCrossRefGoogle Scholar
  110. 110.
    Lin JJ-C, Yamashiro-Matsumura S, Matsumura F. Microfilaments in normal and transformed cells: Changes in the multiple forms of tropomyosin. Cancer Cells 1984; 1:57–65.Google Scholar
  111. 111.
    Warren RH. TGF-α-induced breakdown of stress fibers and degradation of tropomyosin in NRK cells is blocked by a proteosome inhibitor. Exp Cell Res 1997; 236:294–303.PubMedCrossRefGoogle Scholar
  112. 112.
    Hughes JA, Cooke-Yarborough CM, Chadwick NC et al. High-molecular-weight tropomyosins localize to the contractile rings of dividing CNS cells but are absent from malignant pediatric and adult CNS tumors. Glia 2003; 42:25–35.PubMedCrossRefGoogle Scholar
  113. 113.
    Pelham RJJ, Lin JJ-C, Wang Y-L. A high molecular mass nonmuscle tropomyosin isoform stimulates retrograde organelle transport. J Cell Sci 1996; 109:981–989.PubMedGoogle Scholar
  114. 114.
    Warren KS, Lin JL, McDermott JP et al. Forced expression of chimeric human fibroblast tropomyosin mutants affects cytokinesis. J Cell Biol 1995; 129:697–708.PubMedCrossRefGoogle Scholar
  115. 115.
    Heimann K, Percival JM, Weiberger R et al. Specific isoforms of actin-binding proteins on distinct populations of Golgi-derived vesicles. J Biol chem 1999; 274:10743–10750.PubMedCrossRefGoogle Scholar
  116. 116.
    Schevzov G, Gunning P, Jeffrey PL et al. Tropomyosin localization reveals distinct populations of microfilaments in neurites and growth cones. Mol Cellul Neurosci 1997; 8:439–454.CrossRefGoogle Scholar
  117. 117.
    Stehn JR, Schevzov G, O’Neill GM et al. Specialisation of the tropomyosin composition of actin filaments provides new potential targets for chemotherapy. Curr Cancer Drug Targets 2006; 6:245–256.PubMedCrossRefGoogle Scholar
  118. 118.
    Kesari KV, Yoshizaki N, Geng X et al. Externalization of tropomyosin isoform 5 in colon epithelial cells. Clin Exp Immunol 1999; 118:219–227.PubMedCrossRefGoogle Scholar
  119. 119.
    Lin JJ, Lin JL. Assembly of different isoforms of actin and tropomyosin into the skeletal tropomyosinenriched microfilaments during differentiation of muscle cells in vitro. J Cell Biol 1986; 103:2173–2183.PubMedCrossRefGoogle Scholar
  120. 120.
    L’Ecuyer TJ, Schulte D, Lin JJ. Thin filament changes during in vivo rat heart development. Pediatr Res 1991; 30:232–238.PubMedGoogle Scholar
  121. 121.
    Zhu S, Si M-L, Wu H et al. MicrRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 2007; 282:14328–14336.PubMedCrossRefGoogle Scholar
  122. 122.
    Lin JJ-C, Chou CS, Lin JL-C. Monoclonal antibodies against chicken tropomyosin isoforms: production, characterization and application. Hybridoma 1985; 4:223–242.PubMedCrossRefGoogle Scholar
  123. 123.
    Hegmann TE, Lin JL-C, Lin JJ-C. Motility-dependence of the heterogenous staining of culture cells by a monoclonal anti-tropomyosin antibody. J Cell Biol 1988; 106:385–393.PubMedCrossRefGoogle Scholar
  124. 124.
    Hegmann TE, Lin JL-C, Lin JJ-C. Probing the role of nonmuscle tropomyosin isoforms in intracellular granule movement by microinjection of monoclonal antibodies. J Cell Biol 1989; 109:1141–1152.PubMedCrossRefGoogle Scholar
  125. 125.
    Percival JM, Hughes JAI, Brown DL et al. Targeting of a tropomyosin isoform to short microfilaments associated with the Golgi complex. Mol Biol Cell 2004; 15:268–280.PubMedCrossRefGoogle Scholar
  126. 126.
    Cai Y, Biais N, Giannone G et al. Nonmuscle myosin IIA-dependent force inhibits cell spreading and drives F-actin flow. Biophys J 2006; 91:3907–3920.PubMedCrossRefGoogle Scholar
  127. 127.
    Kovar DR. Intracellular motility: myosin and tropomyosin in actin cable flow. Curr Biol 2007; 17: R244–247.PubMedCrossRefGoogle Scholar
  128. 128.
    Collins K, Matsudaira P. Differential regulation of vertebrate myosins I and II. J Cell Sci Suppl 1991; 14:11–16.PubMedGoogle Scholar
  129. 129.
    Bakin AV, Rinehart C, Tomlinson AK et al. p38 mitogen-activated protein kinase is required for TGFβ-mediated fibroblastic transdifferentiation and cell migration. J Cell Sci 2002; 115:3193–3206.PubMedGoogle Scholar
  130. 130.
    Kozma SC, Bogaard MC, Buser K et al. The human c-Kirstein ras gene is activated by a novelmutation in codon 13 in the breastcarcinomacell line MDA-MB321. Nucleic Acids Res 1987; 15:5963–5971.PubMedCrossRefGoogle Scholar
  131. 131.
    Ogata H, Sato H, Takatsuka J et al. Human breast cancer MDA-MB-321 cells fail to express the neurofibromin protein, lack its type 1 mRNA isoform and slow accumulation of P-MAPK and activated Ras. Cancer Lett 2001; 172:159–164.PubMedCrossRefGoogle Scholar
  132. 132.
    Ljungdahl S, Linder S, Franzen B et al. Down-regulation of tropomyosin-2 expression in c-jun-transormed rat fibroblasts involves induction of a MEK1-dependent autocrine loop. Cell Growth Differ 1998; 9:565–573.PubMedGoogle Scholar
  133. 133.
    Shields JM, Mehta H, Pruitt K et al. Opposing roles of the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase cascades in Ras-mediated downregulation of tropomyosin. Mol Cell Biol 2002; 22:2304–2317.PubMedCrossRefGoogle Scholar
  134. 134.
    O’Donoghue PJ. Cryptosporidium and cryptosporidiosis in man and animals. Int J Parasitol 1995; 25:139–195.CrossRefGoogle Scholar
  135. 135.
    Forney JR, DeWald DB, Yang SG et al. A role for host phosphoinositide 3-kinase and cytoskeletal remodeling during Cryptosporidium parvum infection. Infect Immun 1999; 67:844–852.PubMedGoogle Scholar
  136. 136.
    Marcial MA, Madara JL. Cryptosporidium: cellular localization, structural analysis of absorptive cell-parasite membrane-membrane interactions in guinea pigs and suggestion of protozoan transport by M cells. Gastroenterology 1986; 90:583–594.PubMedGoogle Scholar
  137. 137.
    O’Hara SP, Lin JJ. Accumulation of tropomyosin isoform 5 at the infection sites of host cells during Cryptosporidium invasion. Parasitol Res 2006; 99:45–54.PubMedCrossRefGoogle Scholar
  138. 138.
    Finlay BB, Ruschkowski S, Dedhar S. Cytoskeletal rearrangements accompanying salmonella entry into epithelial cells. J Cell Sci 1991; 99(Pt 2):283–296.PubMedGoogle Scholar
  139. 139.
    Gruenheid S, Finlay BB. Microbial pathogenesis and cytoskeletal function. Nature 2003; 422:775–781.PubMedCrossRefGoogle Scholar
  140. 140.
    Eppinga RD, Li Y, Lin JL-C et al. Tropomyosin and caldesmon regulate cytokinesis speed and membrane stability during cell division. Arch Biochem Biophys 2006; 456:161–174.PubMedCrossRefGoogle Scholar
  141. 141.
    Wong K, Wessels D, Krob SL et al. Forced expression of a dominant-negative chimeric tropomyosin causes abnormal motile behavior during cell division. Cell Motil Cytoskel 2000; 45:121–132.CrossRefGoogle Scholar
  142. 142.
    Bharadwaj S, Hitchcock-DeGregori S, Thorburn A et al. N terminus is essential for tropomyosin functions: N-terminal modification disrupts stress fiber organization and abolishes anti-oncogenic effects of tropomyosin-1. J Biol Chem 2004; 279:14039–14048.PubMedCrossRefGoogle Scholar
  143. 143.
    Bharadwaj S, Shah V, Tariq F et al. Amino terminal, but not the carboxy terminal, sequences of tropomyosin-1 are essential for the induction of stress fiber assembly in neoplastic cells. Cancer Lett 2005; 229:253–260.PubMedCrossRefGoogle Scholar
  144. 144.
    Charras GT, Hu CK, Coughlin M et al. Reassembly of contractile actin cortex in cell blebs. J Cell Biol 2006; 175:477–490.PubMedCrossRefGoogle Scholar
  145. 145.
    Nyberg P, Xie L, RK. Endogenous inhibitors of angiogenesis. Cancer Res 2005; 65:3967–3979.PubMedCrossRefGoogle Scholar
  146. 146.
    Sund M, Xie L, Kalluri R. The contribution of vascular basement membranes and extracellular matrix to the mechanics of tumor angiogenesis. APMIS 2004; 112:450–462.PubMedCrossRefGoogle Scholar
  147. 147.
    Browder T, Folkman J, Pirie-Shepard S. The hemostatic system as a regulator of angiogenesis. J Biol Chem 2000; 275:1521–1524.PubMedCrossRefGoogle Scholar
  148. 148.
    Zhang J-C, Claffey K, Sakthivel R et al. Cleaved high molecular weight kininogen promotes endothelial cell apoptosis and inhibits angiogenesis in vivo. FASEB J 2000; 14:2589–2600.PubMedCrossRefGoogle Scholar
  149. 149.
    Zhang J-C, Qi X, Juarez J et al. Inhibition of angiogenesis by two-chain high molecular weight kininogen (HKa) and kininogen-derived polypeptides. Can J Physiol Pharmacol 2002; 80:85–90.PubMedCrossRefGoogle Scholar
  150. 150.
    Joseph K, Ghebrehiwet B, Peerschke EIB et al. Identification of the zinc-dependent endothelial cell binding protein for high molecular weight kininogen and factor XII: Identify with the receptor that binds to the globular “heads” of C1q (gC1q-R). Proc Natl Acad Sci USA 1996; 93:8552–8557.PubMedCrossRefGoogle Scholar
  151. 151.
    Herwald H, Dedio J, Kellner R et al. Isolation and characterization of the kininogen binding protein p33 from endothelial cells. J Biol Chem 1996; 271:13040–13047.PubMedCrossRefGoogle Scholar
  152. 152.
    Hasan AAK, Zisman T, Schmaier AH. Identification of cytokeratin as a binding protein and presentation receptor for kininogens on endothelial cells. Proc Natl Acad Sci USA 1998; 95:3615–3620.PubMedCrossRefGoogle Scholar
  153. 153.
    Colman RW, Pixey RA, Najamunnisa S et al. Binding of high molecular weight kininogen to human endothelial cells is mediated via a site within domains 2+3 of the urokinase receptor. J Clin Invest 1997; 100:1481–1487.PubMedCrossRefGoogle Scholar
  154. 154.
    Renne T, Dedio J, David G et al. High molecular weight kininogen utilizes heparan sulfate proteoglycans for accumulation on endothelial cells. J Biol Chem 2000; 275:33688–33696.PubMedCrossRefGoogle Scholar
  155. 155.
    Zhang J-C, Donate F, Qi X et al. The antiangiogenic activity of cleaved high molecular weight kininogen is mediated through binding to endothelial cell tropomyosin. Proc Natl Acad Sci USA 2002; 99:12224–12229.PubMedCrossRefGoogle Scholar
  156. 156.
    MacDonald NJ, Shivers WY, Narum DL et al. Endostatin binds tropomyosin: A potential modulator of the anti-tumor activity of endostatin. J Biol Chem 2001; 276(27):25190–25196.PubMedCrossRefGoogle Scholar
  157. 157.
    Moroianu J, Fett JW, Riordan JF et al. Actin is a surface component of calf pulmonary artery endothelial cells in culture. Proc Natl Acad Sci USA 1990; 90:3815–3819.CrossRefGoogle Scholar
  158. 158.
    Dudani AK, Ganz PR. Endothelial cell surface actin serves as a binding site for plasminogen, tissue plasminogen activator and lipoprotein(a). Br J Haematol 1996; 95:168–178.PubMedCrossRefGoogle Scholar
  159. 159.
    Dedio J, Muller-Esterl W. Kininogen binding protein p33/gC1qR is localized in the vesicular fraction of endothelial cells. FEBS Lett 1996; 399:255–258.PubMedCrossRefGoogle Scholar
  160. 160.
    Dedio J, Jahnen-Dechent W, Bachmann M et al. The multiligand-binding protein gC1qR, putative C1q receptor, is a mitochondrial protein. J Immunol 1998; 160:3534–3542.PubMedGoogle Scholar
  161. 161.
    Ling Q, Jacovina AT, Deora A et al. Annexin II regulates fibrin homeostasis and neoangiogenesis in vivo. J Clin Invest 2004; 113:38–48.PubMedGoogle Scholar
  162. 162.
    Joseph K, Tholanikunnel BG, Kaplan AP. Heat shock protein 90 catalyzes activation of the prekallikrein-kininogen complex in the absence of factor XII. Proc Natl Acad Sci USA 2002; 99:896–900.PubMedCrossRefGoogle Scholar
  163. 163.
    Taniguchi M, Geng X, Glazier KD et al. Cellular immune response against tropomyosin isoform 5 in ulcerative colitis. Clin Immunol 2001; 101:289–295.PubMedCrossRefGoogle Scholar
  164. 164.
    Ebert EC, Geng X, Glazier KD et al. Autoantibodies against human tropomyosin isoform 5 in ulcerative colitis destroys colonic epithelial cells through antibody and complement-mediated lysis. Cell Immunol 2006; 244:43–49.PubMedCrossRefGoogle Scholar
  165. 165.
    Mirza ZK, Sastri B, Lin JJ-C et al. Autoimmunity against human tropomyosin isoforms in ulcerative colitis. localization of specific human tropomyosin isoforms in the intestine and extraintestinal organs. Inflamm Bowel Dis 2006; 12:1036–1043.PubMedCrossRefGoogle Scholar
  166. 166.
    Cook RK, Blake WT, Rubenstein PA. Removal of the amino-terminal acidic residues of yeast actin; studies in vitro and in vivo. J Biol Chem 1992; 267:9430–9436.PubMedGoogle Scholar
  167. 167.
    Roberts AB, Wakefield LM. The two faces of transforming growth factor β in carcinogenesis. Proc Natl Acad Sci USA 2003; 100:8621–8623.PubMedCrossRefGoogle Scholar
  168. 168.
    Mahesh SP, Li Z, Buggage R et al. Alpha tropomyosin as a self-antigen in patients with Behcet’s disease. Clin Exp Immunol 2005; 140:368–375.PubMedCrossRefGoogle Scholar
  169. 169.
    Dunn SA, Mohteshamzadeh M, Daly AK et al. Altered tropomyosin expression in essential hypertension. Hypertension 2003; 41:347–354.PubMedCrossRefGoogle Scholar
  170. 170.
    Li Q, Dai Y, Guo L et al. Polycystin-2 associates with tropomyosin-1, an actin microfilament component. J Mol Biol 2003; 325:949–962.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2008

Authors and Affiliations

  • Jim Jung-Ching Lin
    • 1
    Email author
  • Robbin D. Eppinga
    • 1
  • Kerri S. Warren
    • 1
  • Keith R. McCrae
    • 2
  1. 1.Department of BiologyUniversity of IowaIowa CityUSA
  2. 2.Department of Medicine Division of Hematology and Oncology School of MedicineCase Western Reserve UniversityClevelandUSA

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