tropomodulin

Summary

Summary: An actin capping protein that binds to the pointed-end of ACTIN. It functions in the presence of TROPOMYOSIN to inhibit microfilament elongation.

Top Publications

  1. Gokhin D, Fowler V. Cytoplasmic gamma-actin and tropomodulin isoforms link to the sarcoplasmic reticulum in skeletal muscle fibers. J Cell Biol. 2011;194:105-20 pubmed publisher
    ..Thus, Tmod3 regulates SR-associated ?(cyto)-actin architecture, mechanically stabilizes the SR via a novel cytoskeletal linkage to sAnk1.5, and maintains the alignment of adjacent myofibrils. ..
  2. Skwarek Maruszewska A, Boczkowska M, Zajac A, Kremneva E, Svitkina T, Dominguez R, et al. Different localizations and cellular behaviors of leiomodin and tropomodulin in mature cardiomyocyte sarcomeres. Mol Biol Cell. 2010;21:3352-61 pubmed publisher
    ..is a muscle-specific F-actin-nucleating protein that is related to the F-actin pointed-end-capping protein tropomodulin (Tmod)...
  3. Sung L, Lin J. Erythrocyte tropomodulin binds to the N-terminus of hTM5, a tropomyosin isoform encoded by the gamma-tropomyosin gene. Biochem Biophys Res Commun. 1994;201:627-34 pubmed
    b>Tropomodulin is a 40.6-kDa protein that binds to one end of the rod-like tropomyosin and inhibits its cooperativity and binding to actin. In myofibrils, tropomodulin has been localized at or near the free end of thin filaments...
  4. Sussman M, BaquƩ S, Uhm C, Daniels M, Price R, Simpson D, et al. Altered expression of tropomodulin in cardiomyocytes disrupts the sarcomeric structure of myofibrils. Circ Res. 1998;82:94-105 pubmed
    b>Tropomodulin is a tropomyosin-binding protein that terminates "pointed-end" actin filament polymerization...
  5. Nowak R, Fischer R, Zoltoski R, Kuszak J, Fowler V. Tropomodulin1 is required for membrane skeleton organization and hexagonal geometry of fiber cells in the mouse lens. J Cell Biol. 2009;186:915-28 pubmed publisher
  6. Kostyukova A, Rapp B, Choy A, Greenfield N, Hitchcock Degregori S. Structural requirements of tropomodulin for tropomyosin binding and actin filament capping. Biochemistry. 2005;44:4905-10 pubmed
    Regulation of actin filament dynamics underlies many cellular functions. Tropomodulin together with tropomyosin can cap the pointed, slowly polymerizing, filament end, inhibiting addition or loss of actin monomers...
  7. Cox P, Fowler V, Xu B, Sweatt J, Paylor R, Zoghbi H. Mice lacking Tropomodulin-2 show enhanced long-term potentiation, hyperactivity, and deficits in learning and memory. Mol Cell Neurosci. 2003;23:1-12 pubmed
    ..tropomodulins could play a role in synaptic plasticity, learning, memory, or behavior, we created mice lacking Tropomodulin-2 (Tmod2), which is highly expressed in neuronal structures...
  8. Lu S, Symersky J, Li S, Carson M, Chen L, Meehan E, et al. Structural genomics of Caenorhabditis elegans: crystal structure of the tropomodulin C-terminal domain. Proteins. 2004;56:384-6 pubmed
  9. Uversky V, Shah S, Gritsyna Y, Hitchcock Degregori S, Kostyukova A. Systematic analysis of tropomodulin/tropomyosin interactions uncovers fine-tuned binding specificity of intrinsically disordered proteins. J Mol Recognit. 2011;24:647-55 pubmed publisher
    ..In this study we undertook a systematic analysis of the specificity of the tropomodulin (Tmod) interaction with tropomyosin (TM) to show that affinities of different Tmod isoforms to TM are isoform-..

More Information

Publications62

  1. McKeown C, Nowak R, Moyer J, Sussman M, Fowler V. Tropomodulin1 is required in the heart but not the yolk sac for mouse embryonic development. Circ Res. 2008;103:1241-8 pubmed publisher
    b>Tropomodulin (Tmod)1 caps the pointed ends of actin filaments in sarcomeres of striated muscle myofibrils and in the erythrocyte membrane skeleton...
  2. Kostyukova A, Hitchcock Degregori S, Greenfield N. Molecular basis of tropomyosin binding to tropomodulin, an actin-capping protein. J Mol Biol. 2007;372:608-18 pubmed
    The tropomodulin (Tmod) family of proteins that cap the pointed, slow-growing end of actin filaments require tropomyosin (TM) for optimal function...
  3. Kostyukova A, Maeda K, Yamauchi E, Krieger I, Maeda Y. Domain structure of tropomodulin: distinct properties of the N-terminal and C-terminal halves. Eur J Biochem. 2000;267:6470-5 pubmed
    The structure of tropomodulin, the unique capping protein for the pointed end (the slow-growing end) of an actin filament, was studied...
  4. Mardahl Dumesnil M, Fowler V. Thin filaments elongate from their pointed ends during myofibril assembly in Drosophila indirect flight muscle. J Cell Biol. 2001;155:1043-53 pubmed
    b>Tropomodulin (Tmod) is an actin pointed-end capping protein that regulates actin dynamics at thin filament pointed ends in striated muscle...
  5. Ito M, Swanson B, Sussman M, Kedes L, Lyons G. Cloning of tropomodulin cDNA and localization of gene transcripts during mouse embryogenesis. Dev Biol. 1995;167:317-28 pubmed
    b>Tropomodulin (Tmod) is a tropomyosin-binding protein involved in the structuring of actin filaments...
  6. Fritz Six K, Cox P, Fischer R, Xu B, Gregorio C, Zoghbi H, et al. Aberrant myofibril assembly in tropomodulin1 null mice leads to aborted heart development and embryonic lethality. J Cell Biol. 2003;163:1033-44 pubmed
    ..We conclude that Tmod1 is required for regulation of actin filament lengths and myofibril maturation; this is critical for heart morphogenesis during embryonic development. ..
  7. Porro F, Costessi L, Marro M, Baralle F, Muro A. The erythrocyte skeletons of beta-adducin deficient mice have altered levels of tropomyosin, tropomodulin and EcapZ. FEBS Lett. 2004;576:36-40 pubmed
    ..We also detected upregulation of tropomodulin and downregulation of alpha-tropomyosin and actin...
  8. Stevenson T, Mercer K, Cox E, Szewczyk N, Conley C, HARDIN J, et al. unc-94 encodes a tropomodulin in Caenorhabditis elegans. J Mol Biol. 2007;374:936-50 pubmed
    ..Multiple lines of evidence prove that unc-94 encodes a tropomodulin, a conserved protein known from other systems to bind to both actin and tropomyosin at the pointed ends of ..
  9. Cox P, Zoghbi H. Sequencing, expression analysis, and mapping of three unique human tropomodulin genes and their mouse orthologs. Genomics. 2000;63:97-107 pubmed
    b>Tropomodulin (TMOD) is the actin-capping protein for the slow-growing end of filamentous actin, and a neuronal-specific isoform, neuronal tropomodulin (NTMOD), is the major binding protein to brain tropomyosin in rat...
  10. Greenfield N, Fowler V. Tropomyosin requires an intact N-terminal coiled coil to interact with tropomodulin. Biophys J. 2002;82:2580-91 pubmed
  11. Gokhin D, Fowler V. Tropomodulin capping of actin filaments in striated muscle development and physiology. J Biomed Biotechnol. 2011;2011:103069 pubmed publisher
    ..We also discuss emerging functions for Tmods in the sarcoplasmic reticulum. This paper provides abundant evidence that Tmods are key structural regulators of striated muscle cytoarchitecture and physiology. ..
  12. Mudry R, Perry C, Richards M, Fowler V, Gregorio C. The interaction of tropomodulin with tropomyosin stabilizes thin filaments in cardiac myocytes. J Cell Biol. 2003;162:1057-68 pubmed
  13. Babcock G, Fowler V. Isoform-specific interaction of tropomodulin with skeletal muscle and erythrocyte tropomyosins. J Biol Chem. 1994;269:27510-8 pubmed
    b>Tropomodulin is a tropomyosin-binding protein that localizes to the pointed end of striated muscle thin filaments and caps the pointed end of tropomyosin-actin filaments in vitro...
  14. Rao J, Madasu Y, Dominguez R. Mechanism of actin filament pointed-end capping by tropomodulin. Science. 2014;345:463-7 pubmed publisher
    ..Whereas several proteins cap the rapidly growing barbed end, tropomodulin (Tmod) is the only protein known to cap the slowly growing pointed end...
  15. Fischer R, Fritz Six K, Fowler V. Pointed-end capping by tropomodulin3 negatively regulates endothelial cell motility. J Cell Biol. 2003;161:371-80 pubmed
    ..We describe here a previously uncharacterized tropomodulin (Tmod) isoform, Tmod3, which is widely expressed in human tissues and is present in human microvascular ..
  16. Chu X, Thompson D, Yee L, Sung L. Genomic organization of mouse and human erythrocyte tropomodulin genes encoding the pointed end capping protein for the actin filaments. Gene. 2000;256:271-81 pubmed
    Erythrocyte tropomodulin (E-Tmod), a globular protein of 359 residues, is highly expressed in the erythrocyte, heart and skeletal muscle...
  17. Tsukada T, Kotlyanskaya L, Huynh R, Desai B, Novak S, Kajava A, et al. Identification of residues within tropomodulin-1 responsible for its localization at the pointed ends of the actin filaments in cardiac myocytes. J Biol Chem. 2011;286:2194-204 pubmed publisher
    b>Tropomodulin is a tropomyosin-dependent actin filament capping protein involved in the structural formation of thin filaments and in the regulation of their lengths through its localization at the pointed ends of actin filaments...
  18. Matsuzaka Y, Okamoto K, Mabuchi T, Iizuka M, Ozawa A, Oka A, et al. Identification, expression analysis and polymorphism of a novel RLTPR gene encoding a RGD motif, tropomodulin domain and proline/leucine-rich regions. Gene. 2004;343:291-304 pubmed
    ..acid sequence contains four distinct structural regions, an RGD motif, a leucine-rich repeat (LRR) region, a tropomodulin domain, and a proline-rich domain...
  19. Ilkovski B, Mokbel N, Lewis R, Walker K, Nowak K, Domazetovska A, et al. Disease severity and thin filament regulation in M9R TPM3 nemaline myopathy. J Neuropathol Exp Neurol. 2008;67:867-77 pubmed publisher
    ..Using recombinant proteins and far Western blot, we demonstrated a higher affinity of tropomodulin for alpha-tropomyosin(slow) compared with beta-tropomyosin; the M9R substitution within alpha-tropomyosin(slow) ..
  20. Sussman M, Welch S, Cambon N, Klevitsky R, Hewett T, Price R, et al. Myofibril degeneration caused by tropomodulin overexpression leads to dilated cardiomyopathy in juvenile mice. J Clin Invest. 1998;101:51-61 pubmed
    ..Myofibril degeneration was induced by overexpression of tropomodulin, a component of the thin filament complex which determines and maintains sarcomeric actin filament length...
  21. Castillo A, Nowak R, Littlefield K, Fowler V, Littlefield R. A nebulin ruler does not dictate thin filament lengths. Biophys J. 2009;96:1856-65 pubmed publisher
    ..The hypothesis that a nebulin ruler mechanism specifies thin filament lengths by targeting where tropomodulin (Tmod) caps the slow-growing, pointed end has not been rigorously tested...
  22. Gokhin D, Lewis R, McKeown C, Nowak R, Kim N, Littlefield R, et al. Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology. J Cell Biol. 2010;189:95-109 pubmed publisher
    ..Thus, Tmod3 and -4 compensate for the absence of Tmod1 structurally but not functionally. We conclude that Tmod1 is a novel regulator of skeletal muscle physiology. ..
  23. Conley C. Leiomodin and tropomodulin in smooth muscle. Am J Physiol Cell Physiol. 2001;280:C1645-56 pubmed
    ..b>Tropomodulin (Tmod) and smooth muscle leiomodin (SM-Lmod) have been found in many tissues containing smooth muscle by ..
  24. Moyer J, Nowak R, Kim N, Larkin S, Peters L, Hartwig J, et al. Tropomodulin 1-null mice have a mild spherocytic elliptocytosis with appearance of tropomodulin 3 in red blood cells and disruption of the membrane skeleton. Blood. 2010;116:2590-9 pubmed publisher
    The short actin filaments in the red blood cell (RBC) membrane skeleton are capped at their pointed ends by tropomodulin 1 (Tmod1) and coated with tropomyosin (TM) along their length...
  25. Greenfield N, Kostyukova A, Hitchcock Degregori S. Structure and tropomyosin binding properties of the N-terminal capping domain of tropomodulin 1. Biophys J. 2005;88:372-83 pubmed
    Two families of actin regulatory proteins are the tropomodulins and tropomyosins. Tropomodulin binds to tropomyosin (TM) and to the pointed end of actin filaments and "caps" the pointed end (i.e...
  26. Rho S, Chun T, Lee S, Park K, Lee J. The interaction between E-tropomodulin and thymosin beta-10 rescues tumor cells from thymosin beta-10 mediated apoptosis by restoring actin architecture. FEBS Lett. 2004;557:57-63 pubmed
    ..The selected protein was human E-tropomodulin (E-Tmod), another component of the actin binding proteins...
  27. Yamashiro S, Gokhin D, Kimura S, Nowak R, Fowler V. Tropomodulins: pointed-end capping proteins that regulate actin filament architecture in diverse cell types. Cytoskeleton (Hoboken). 2012;69:337-70 pubmed publisher
    ..Tmod-based stabilization and organization of intracellular actin filament networks provide key insights into how the emergent properties of the actin cytoskeleton drive tissue morphogenesis and physiology. ..
  28. Conley C, Fritz Six K, Almenar Queralt A, Fowler V. Leiomodins: larger members of the tropomodulin (Tmod) gene family. Genomics. 2001;73:127-39 pubmed
    ..64-kDa autoantigen D1 or 1D, first identified as a potential autoantigen in Graves' disease, is similar to the tropomodulin (Tmod) family of actin filament pointed end-capping proteins...
  29. Kostyukova A, Hitchcock Degregori S. Effect of the structure of the N terminus of tropomyosin on tropomodulin function. J Biol Chem. 2004;279:5066-71 pubmed
    ..An even shorter fragment, Tmod1-(1-48), bound tropomyosin but did not influence actin filament elongation. Tropomyosin-Tmod may function to locally regulate cytoskeletal dynamics in cells by stabilizing actin filaments. ..
  30. Pappas C, Krieg P, Gregorio C. Nebulin regulates actin filament lengths by a stabilization mechanism. J Cell Biol. 2010;189:859-70 pubmed publisher
    ..e., recovered loss of endogenous nebulin). Thus, nebulin regulates thin filament architecture by a mechanism that includes stabilizing the filaments and preventing actin depolymerization. ..
  31. Kong K, Kedes L. Leucine 135 of tropomodulin-1 regulates its association with tropomyosin, its cellular localization, and the integrity of sarcomeres. J Biol Chem. 2006;281:9589-99 pubmed
    b>Tropomodulin-1 (Tmod-1) is a well defined actin-capping protein that interacts with tropomyosin (TM) at the pointed end of actin filaments...
  32. Fischer R, Yarmola E, Weber K, Speicher K, Speicher D, Bubb M, et al. Tropomodulin 3 binds to actin monomers. J Biol Chem. 2006;281:36454-65 pubmed
    ..The ubiquitous pointed end capping protein Tmod3 (tropomodulin 3) acts as a negative regulator of cell migration, yet mechanisms behind its cellular functions are not ..
  33. McLean M, Zajdel R, Dube S, Thurston H, Dube D. Tropomodulin expression in developing hearts of normal and cardiac mutant Mexican axolotl. Cardiovasc Toxicol. 2006;6:85-98 pubmed
    ..the myofibril assembly process in mutant hearts using a relatively new late marker for thin filament assembly, tropomodulin (Tmod). This is, to the best of our knowledge, the first report of tropomodulin in an amphibian system...
  34. Watakabe A, Kobayashi R, Helfman D. N-tropomodulin: a novel isoform of tropomodulin identified as the major binding protein to brain tropomyosin. J Cell Sci. 1996;109 ( Pt 9):2299-310 pubmed
    ..Peptide sequencing as well as immunoblotting showed that one of the two proteins is identical to tropomodulin, a tropomyosin-binding protein originally identified in erythrocytes...
  35. Chu X, Chen J, Reedy M, Vera C, Sung K, Sung L. E-Tmod capping of actin filaments at the slow-growing end is required to establish mouse embryonic circulation. Am J Physiol Heart Circ Physiol. 2003;284:H1827-38 pubmed
    Tropomodulins are a family of proteins that cap the slow-growing end of actin filaments. Erythrocyte tropomodulin (E-Tmod) stabilizes short actin protofilaments in erythrocytes and caps longer sarcomeric actin filaments in striated ..
  36. Ursitti J, Fowler V. Immunolocalization of tropomodulin, tropomyosin and actin in spread human erythrocyte skeletons. J Cell Sci. 1994;107 ( Pt 6):1633-9 pubmed
    ..are proposed to be stabilized and limited by association with tropomyosin and the tropomyosin-binding protein, tropomodulin. Here, we use immunogold labelling followed by negative staining to specifically localize tropomodulin, ..
  37. Ochala J, Gokhin D, Iwamoto H, Fowler V. Pointed-end capping by tropomodulin modulates actomyosin crossbridge formation in skeletal muscle fibers. FASEB J. 2014;28:408-15 pubmed publisher
    In skeletal muscle, thick and thin filaments are arranged in a myofibrillar lattice. Tropomodulin 1 (Tmod1) is a pointed-end capping and tropomyosin-binding protein that controls thin-filament assembly, stability, and lengths...
  38. Kostyukova A, Choy A, Rapp B. Tropomodulin binds two tropomyosins: a novel model for actin filament capping. Biochemistry. 2006;45:12068-75 pubmed
    b>Tropomodulin, a tropomyosin-binding protein, caps the slow-growing (pointed) end of the actin filament regulating its dynamics. Tropomodulin, therefore, is important for determining cell morphology, cell movement, and muscle contraction...
  39. Chereau D, Boczkowska M, Skwarek Maruszewska A, Fujiwara I, Hayes D, Rebowski G, et al. Leiomodin is an actin filament nucleator in muscle cells. Science. 2008;320:239-43 pubmed publisher
    ..Leiomodin shared two actin-binding sites with the filament pointed end-capping protein tropomodulin: a flexible N-terminal region and a leucine-rich repeat domain...
  40. Sussman M, Welch S, Gude N, Khoury P, Daniels S, Kirkpatrick D, et al. Pathogenesis of dilated cardiomyopathy: molecular, structural, and population analyses in tropomodulin-overexpressing transgenic mice. Am J Pathol. 1999;155:2101-13 pubmed
    ..Previously unexplored structural and molecular events that precede and initiate dilation can now be studied in tropomodulin-overexpressing transgenic (TOT) mice exhibiting progressive dilated cardiomyopathy...
  41. Vera C, Lao J, Hamelberg D, Sung L. Mapping the tropomyosin isoform 5 binding site on human erythrocyte tropomodulin: further insights into E-Tmod/TM5 interaction. Arch Biochem Biophys. 2005;444:130-8 pubmed
    ..This length may be in part attributed to a "molecular ruler" made of erythrocyte tropomodulin (E-Tmod) and tropomyosin (TM) isoforms 5 or 5b...
  42. Ono Y, Schwach C, Antin P, Gregorio C. Disruption in the tropomodulin1 (Tmod1) gene compromises cardiomyocyte development in murine embryonic stem cells by arresting myofibril maturation. Dev Biol. 2005;282:336-48 pubmed
  43. Sussman M, Welch S, Walker A, Klevitsky R, Hewett T, Witt S, et al. Hypertrophic defect unmasked by calcineurin expression in asymptomatic tropomodulin overexpressing transgenic mice. Cardiovasc Res. 2000;46:90-101 pubmed
    ..two cardiomyopathic transgenic mouse lines which develop either hypertrophy (calcineurin-mediated) or dilation (tropomodulin-mediated)...
  44. Fowler V, Greenfield N, Moyer J. Tropomodulin contains two actin filament pointed end-capping domains. J Biol Chem. 2003;278:40000-9 pubmed
    b>Tropomodulin 1 (Tmod1) is a approximately 40-kDa tropomyosin binding and actin filament pointed end-capping protein that regulates pointed end dynamics and controls thin filament length in striated muscle...
  45. Dye C, Lee J, Atkinson R, Brewster R, Han P, Bellen H. The Drosophila sanpodo gene controls sibling cell fate and encodes a tropomodulin homolog, an actin/tropomyosin-associated protein. Development. 1998;125:1845-56 pubmed
    ..Genetic interaction studies show that sanpodo is epistatic to numb. sanpodo encodes a homolog of tropomodulin, an actin/tropomyosin-associated protein...
  46. Weber K, Fischer R, Fowler V. Tmod3 regulates polarized epithelial cell morphology. J Cell Sci. 2007;120:3625-32 pubmed
    ..We propose that Tmod3-capped tropomyosin-actin filaments provide crucial links in the spectrin membrane skeleton of polarized epithelial cells, enabling the membrane skeleton to maintain cell shape. ..
  47. Kong K, Kedes L. Cytoplasmic nuclear transfer of the actin-capping protein tropomodulin. J Biol Chem. 2004;279:30856-64 pubmed
    b>Tropomodulin (Tmod) is a cytoskeletal actin-capping protein that interacts with tropomyosin at the pointed end of actin filaments. E-Tmod is an isoform that expresses predominantly in cardiac cells and slow skeletal muscle fibers...
  48. Fischer R, Quinlan R, Fowler V. Tropomodulin binds to filensin intermediate filaments. FEBS Lett. 2003;547:228-32 pubmed
    b>Tropomodulin (Tmod) is an actin filament pointed end capping protein found in the membrane skeleton of lens fiber cells...
  49. Welch S, Plank D, Witt S, Glascock B, Schaefer E, Chimenti S, et al. Cardiac-specific IGF-1 expression attenuates dilated cardiomyopathy in tropomodulin-overexpressing transgenic mice. Circ Res. 2002;90:641-8 pubmed
    ..Hemodynamic, structural, and cellular parameters of the heart were compared between nontransgenic, tropomodulin-overexpressing cardiomyopathic, and the hybrid tropomodulin/IGF-1-overexpressing mice...
  50. Vera C, Sood A, Gao K, Yee L, Lin J, Sung L. 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 pubmed
    b>Tropomodulin is a globular protein that caps the pointed end of actin filaments by complexing with the N-terminus of a tropomyosin (TM) molecule. TM consists of coiled coils except for the N-terminus, which may be globular...
  51. Sung L, Fowler V, Lambert K, Sussman M, Karr D, Chien S. Molecular cloning and characterization of human fetal liver tropomodulin. A tropomyosin-binding protein. J Biol Chem. 1992;267:2616-21 pubmed
    Human erythrocyte tropomodulin is a novel tropomyosin regulatory protein that binds to the end of erythrocyte tropomyosin and blocks heat-to-tail association of tropomyosin along actin filaments...
  52. Nowak R, Fowler V. Tropomodulin 1 constrains fiber cell geometry during elongation and maturation in the lens cortex. J Histochem Cytochem. 2012;60:414-27 pubmed publisher
    Lens fiber cells exhibit a high degree of hexagonal packing geometry, determined partly by tropomodulin 1 (Tmod1), which stabilizes the spectrin-actin network on lens fiber cell membranes...
  53. Wagner L, Fowler V, Takemoto D. The interaction and phosphorylation of tropomodulin by protein kinase Calpha in N/N 1003A lens epithelial cells. Mol Vis. 2002;8:394-406 pubmed
    b>Tropomodulin, a tropomyosin and actin-binding protein stabilizes tropomyosin-actin filaments and is important in maintaining the elongated shape of lens fiber cells...