Ttn

Summary

Gene Symbol: Ttn
Description: titin
Alias: 1100001C23Rik, 2310036G12Rik, 2310057K23Rik, 2310074I15Rik, AF006999, AV006427, D330041I19Rik, D830007G01Rik, L56, mdm, shru, titin, connectin, ttn
Species: mouse
Products:     Ttn

Top Publications

  1. Ottenheijm C, Hidalgo C, Rost K, Gotthardt M, Granzier H. Altered contractility of skeletal muscle in mice deficient in titin's M-band region. J Mol Biol. 2009;393:10-26 pubmed publisher
    We investigated the contractile phenotype of skeletal muscle deficient in exons MEx1 and MEx2 (KO) of the titin M-band by using the cre-lox recombination system and a multidisciplinary physiological approach to study skeletal muscle ..
  2. Laure L, Daniele N, Suel L, Marchand S, Aubert S, Bourg N, et al. A new pathway encompassing calpain 3 and its newly identified substrate cardiac ankyrin repeat protein is involved in the regulation of the nuclear factor-?B pathway in skeletal muscle. FEBS J. 2010;277:4322-37 pubmed publisher
    ..CARP), and the calpain 3 protease was identified in the N2A elastic region of the giant sarcomeric protein titin. The present study aimed to investigate the function(s) of this complex in the skeletal muscle...
  3. Granzier H, Radke M, Peng J, Westermann D, Nelson O, Rost K, et al. Truncation of titin's elastic PEVK region leads to cardiomyopathy with diastolic dysfunction. Circ Res. 2009;105:557-64 pubmed publisher
    The giant protein titin plays key roles in myofilament assembly and determines the passive mechanical properties of the sarcomere. The cardiac titin molecule has 2 mayor elastic elements, the N2B and the PEVK region...
  4. Kramerova I, Kudryashova E, Tidball J, Spencer M. Null mutation of calpain 3 (p94) in mice causes abnormal sarcomere formation in vivo and in vitro. Hum Mol Genet. 2004;13:1373-88 pubmed
    The giant protein titin serves a primary role as a scaffold for sarcomere assembly; however, proteins that mediate this remodeling have not been identified...
  5. Hayashi C, Ono Y, Doi N, Kitamura F, Tagami M, Mineki R, et al. Multiple molecular interactions implicate the connectin/titin N2A region as a modulating scaffold for p94/calpain 3 activity in skeletal muscle. J Biol Chem. 2008;283:14801-14 pubmed publisher
    ..In addition, a small in-frame deletion in the N2A region of connectin/titin that impairs p94-connectin interaction causes a severe muscular dystrophy (mdm) in mice...
  6. Witt C, Ono Y, Puschmann E, McNabb M, Wu Y, Gotthardt M, et al. Induction and myofibrillar targeting of CARP, and suppression of the Nkx2.5 pathway in the MDM mouse with impaired titin-based signaling. J Mol Biol. 2004;336:145-54 pubmed
    ..mdm) is a recessive mouse mutation that is caused by a small deletion in the giant elastic muscle protein titin. Homozygous mdm/mdm mice develop a progressive muscular dystrophy, leading to death at approximately 2 months of ..
  7. Kolmerer B, Olivieri N, Witt C, Herrmann B, Labeit S. Genomic organization of M line titin and its tissue-specific expression in two distinct isoforms. J Mol Biol. 1996;256:556-63 pubmed
    b>Titin is a 3000 kDa large protein of vertebrate striated muscle which extends from Z discs to M lines...
  8. Ali M, Cho W, Hudson B, Kassiri Z, Granzier H, Schulz R. Titin is a target of matrix metalloproteinase-2: implications in myocardial ischemia/reperfusion injury. Circulation. 2010;122:2039-47 pubmed publisher
    b>Titin is the largest mammalian (?3000 to 4000 kDa) and myofilament protein that acts as a molecular spring in the cardiac sarcomere and determines systolic and diastolic function...
  9. Gotthardt M, Hammer R, Hubner N, Monti J, Witt C, McNabb M, et al. Conditional expression of mutant M-line titins results in cardiomyopathy with altered sarcomere structure. J Biol Chem. 2003;278:6059-65 pubmed
    b>Titin is a giant protein responsible for muscle elasticity and provides a scaffold for several sarcomeric proteins, including the novel titin-binding protein MURF-1, which binds near the titin M-line region...

More Information

Publications84

  1. Gregorio C, Trombitas K, Centner T, Kolmerer B, Stier G, Kunke K, et al. The NH2 terminus of titin spans the Z-disc: its interaction with a novel 19-kD ligand (T-cap) is required for sarcomeric integrity. J Cell Biol. 1998;143:1013-27 pubmed
    b>Titin is a giant elastic protein in vertebrate striated muscles with an unprecedented molecular mass of 3-4 megadaltons. Single molecules of titin extend from the Z-line to the M-line...
  2. Garvey S, Rajan C, Lerner A, Frankel W, Cox G. The muscular dystrophy with myositis (mdm) mouse mutation disrupts a skeletal muscle-specific domain of titin. Genomics. 2002;79:146-9 pubmed
    ..identification of the mdm mutation as a complex rearrangement that includes a deletion and a LINE insertion in the titin (Ttn) gene...
  3. Radke M, Peng J, Wu Y, McNabb M, Nelson O, Granzier H, et al. Targeted deletion of titin N2B region leads to diastolic dysfunction and cardiac atrophy. Proc Natl Acad Sci U S A. 2007;104:3444-9 pubmed
    b>Titin is a giant protein that is in charge of the assembly and passive mechanical properties of the sarcomere...
  4. Hidalgo C, Hudson B, Bogomolovas J, Zhu Y, Anderson B, Greaser M, et al. PKC phosphorylation of titin's PEVK element: a novel and conserved pathway for modulating myocardial stiffness. Circ Res. 2009;105:631-8, 17 p following 638 pubmed publisher
    ..Myocardial sarcomeres also contain a third myofilament, titin, and it is unknown whether titin can be phosphorylated by PKC and whether it affects passive tension...
  5. Weinert S, Bergmann N, Luo X, Erdmann B, Gotthardt M. M line-deficient titin causes cardiac lethality through impaired maturation of the sarcomere. J Cell Biol. 2006;173:559-70 pubmed
    b>Titin, the largest protein known to date, has been linked to sarcomere assembly and function through its elastic adaptor and signaling domains...
  6. May S, Stewart N, Chang W, Peterson A. A Titin mutation defines roles for circulation in endothelial morphogenesis. Dev Biol. 2004;270:31-46 pubmed
    ..here the identification of a recessive mouse mutation termed shrunken-head (shru) that disrupts function of the Titin gene...
  7. Miller G, Musa H, Gautel M, Peckham M. A targeted deletion of the C-terminal end of titin, including the titin kinase domain, impairs myofibrillogenesis. J Cell Sci. 2003;116:4811-9 pubmed
    b>Titin is the largest protein known, and is essential for organising muscle sarcomeres. It has many domains with a variety of functions, and stretches from the Z-line to the M-line in the muscle sarcomere...
  8. Bang M, Centner T, Fornoff F, Geach A, Gotthardt M, McNabb M, et al. The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system. Circ Res. 2001;89:1065-72 pubmed
    b>Titin is a giant vertebrate striated muscle protein with critical importance for myofibril elasticity and structural integrity...
  9. Labeit S, Gautel M, Lakey A, Trinick J. Towards a molecular understanding of titin. EMBO J. 1992;11:1711-6 pubmed
    b>Titin is at present the largest known protein (M(r) 3000 kDa) and its expression is restricted to vertebrate striated muscle. Single molecules span from M- to Z-lines and therefore over 1 micron...
  10. Chung C, Hutchinson K, Methawasin M, Saripalli C, Smith J, Hidalgo C, et al. Shortening of the elastic tandem immunoglobulin segment of titin leads to diastolic dysfunction. Circulation. 2013;128:19-28 pubmed publisher
    ..b>Titin is the main determinant of cellular passive stiffness...
  11. Gramlich M, Michely B, Krohne C, Heuser A, Erdmann B, Klaassen S, et al. Stress-induced dilated cardiomyopathy in a knock-in mouse model mimicking human titin-based disease. J Mol Cell Cardiol. 2009;47:352-8 pubmed publisher
    ..43628insAT) and generated a titin knock-in mouse model mimicking the c.43628insAT allele...
  12. Pelikan R, Iwata J, Suzuki A, Chai Y, Hacia J. Identification of candidate downstream targets of TGF? signaling during palate development by genome-wide transcript profiling. J Cell Biochem. 2013;114:796-807 pubmed publisher
  13. Barbosky L, Lawrence D, Karunamuni G, Wikenheiser J, Doughman Y, Visconti R, et al. Apoptosis in the developing mouse heart. Dev Dyn. 2006;235:2592-602 pubmed
    ..These findings suggest that cardiomyocyte apoptosis is an evolutionarily conserved mechanism for normal morphogenesis of the outflow tract myocardium in avian and mammalian species. ..
  14. Taylor R, Grieco D, Clarke G, McInnes R, Taylor B. Identification of the mutation in murine histidinemia (his) and genetic mapping of the murine histidase locus (Hal) on chromosome 10. Genomics. 1993;16:231-40 pubmed
    ..These studies indicate that the R322Q allele reduces the stability of histidase, position Hal on the Chromosome 10 linkage map, and provide further evidence that Hsd is allelic to Hal. ..
  15. Lewandowski S, Janardhan H, Smee K, Bachman M, Sun Z, Lazar M, et al. Histone deacetylase 3 modulates Tbx5 activity to regulate early cardiogenesis. Hum Mol Genet. 2014;23:3801-9 pubmed publisher
    ..These findings reveal that Hdac3 plays a critical role in cardiac progenitor cells to regulate early cardiogenesis. ..
  16. Chen M, Li S, Lam W, Ho Y, Ha S, Chan G, et al. Left ventricular torsional mechanics and myocardial iron load in beta-thalassaemia major: a potential role of titin degradation. BMC Cardiovasc Disord. 2014;14:49 pubmed publisher
    ..B6D2F1 mouse models, we further determined the impact of iron load on proteolysis of the giant sarcomeric protein titin. In 44 thalassaemia patients aged 25 ± 7 years and 38 healthy subjects, LV torsion and twisting velocities were ..
  17. Nguyen A, Xiao B, Neppl R, Kallin E, Li J, Chen T, et al. DOT1L regulates dystrophin expression and is critical for cardiac function. Genes Dev. 2011;25:263-74 pubmed publisher
    ..In addition, our study may open new avenues for the diagnosis and treatment of human heart disease. ..
  18. Darwich R, Li W, Yamak A, Komati H, Andelfinger G, Sun K, et al. KLF13 is a genetic modifier of the Holt-Oram syndrome gene TBX5. Hum Mol Genet. 2017;26:942-954 pubmed publisher
    ..The data also suggest that, in human, KLF13 may be a genetic modifier of the Holt-Oram Syndrome gene TBX5. ..
  19. Hudson B, Hidalgo C, Saripalli C, Granzier H. Hyperphosphorylation of mouse cardiac titin contributes to transverse aortic constriction-induced diastolic dysfunction. Circ Res. 2011;109:858-66 pubmed publisher
    Mechanisms underlying diastolic dysfunction need to be better understood. To study the role of titin in diastolic dysfunction using a mouse model of experimental heart failure induced by transverse aortic constriction...
  20. Peng J, Raddatz K, Labeit S, Granzier H, Gotthardt M. Muscle atrophy in titin M-line deficient mice. J Muscle Res Cell Motil. 2005;26:381-8 pubmed
    We investigated the response to deletion of the titin M-line region in striated muscle, using a titin knockout model and a range of techniques that include histology, in situ hybridization, electron microscopy, and 2D gel analysis...
  21. Chung C, Granzier H. Contribution of titin and extracellular matrix to passive pressure and measurement of sarcomere length in the mouse left ventricle. J Mol Cell Cardiol. 2011;50:731-9 pubmed publisher
    It remains to be established to what degree titin and the extracellular matrix (ECM) contribute to passive pressure in the left ventricle (LV)...
  22. Hirschy A, Schatzmann F, Ehler E, Perriard J. Establishment of cardiac cytoarchitecture in the developing mouse heart. Dev Biol. 2006;289:430-41 pubmed
    ..These observations help to understand the mechanisms that lead to the formation of a functional heart during development at a cellular level. ..
  23. Xing X, Li Q, Sun H, Fu X, Zhan F, Huang X, et al. The discovery of novel protein-coding features in mouse genome based on mass spectrometry data. Genomics. 2011;98:343-51 pubmed publisher
    ..The approach in the current work can provide substantial evidences for eukaryote genome annotation in encoding genes. ..
  24. Bang M. Animal Models of Congenital Cardiomyopathies Associated With Mutations in Z-Line Proteins. J Cell Physiol. 2017;232:38-52 pubmed publisher
    ..Pros and cons of mouse models will be discussed and a future outlook will be given. J. Cell. Physiol. 232: 38-52, 2017. © 2016 Wiley Periodicals, Inc. ..
  25. Monroy J, Powers K, Pace C, Uyeno T, Nishikawa K. Effects of activation on the elastic properties of intact soleus muscles with a deletion in titin. J Exp Biol. 2017;220:828-836 pubmed publisher
    b>Titin has long been known to contribute to muscle passive tension...
  26. Rossi E, Faiella A, Zeviani M, Labeit S, Floridia G, Brunelli S, et al. Order of six loci at 2q24-q31 and orientation of the HOXD locus. Genomics. 1994;24:34-40 pubmed
    ..homeobox genes related to the Drosophila distal-less gene; and TTN and NEB, the genes for the two giant molecules titin and nebulin, both involved in the sarcomere structure, have been previously mapped to human 2q31-q32 and to mouse ..
  27. Braun T, Bober E, Rudnicki M, Jaenisch R, Arnold H. MyoD expression marks the onset of skeletal myogenesis in Myf-5 mutant mice. Development. 1994;120:3083-92 pubmed
    ..0 wild-type and mutant mice indicating that myogenic factor expression at the level of somites is not a prerequisite for determination and subsequent migration of limb precursor cells. ..
  28. Granzier H, Hutchinson K, Tonino P, Methawasin M, Li F, Slater R, et al. Deleting titin's I-band/A-band junction reveals critical roles for titin in biomechanical sensing and cardiac function. Proc Natl Acad Sci U S A. 2014;111:14589-94 pubmed publisher
    b>Titin, the largest protein known, forms a giant filament in muscle where it spans the half sarcomere from Z disk to M band...
  29. Gramlich M, Pane L, Zhou Q, Chen Z, Murgia M, Schötterl S, et al. Antisense-mediated exon skipping: a therapeutic strategy for titin-based dilated cardiomyopathy. EMBO Mol Med. 2015;7:562-76 pubmed publisher
    Frameshift mutations in the TTN gene encoding titin are a major cause for inherited forms of dilated cardiomyopathy (DCM), a heart disease characterized by ventricular dilatation, systolic dysfunction, and progressive heart failure...
  30. Labeit S, Barlow D, Gautel M, Gibson T, Holt J, Hsieh C, et al. A regular pattern of two types of 100-residue motif in the sequence of titin. Nature. 1990;345:273-6 pubmed
    b>Titin is the largest polypeptide yet described (relative molecular mass approximately 3 x 10(6); refs 1, 2) and an abundant protein of striated muscle. Its molecules are string-like and in vivo span from the M to Z-lines...
  31. Lee E, Nedrud J, Schemmel P, Gotthardt M, Irving T, Granzier H. Calcium sensitivity and myofilament lattice structure in titin N2B KO mice. Arch Biochem Biophys. 2013;535:76-83 pubmed publisher
    ..Here the effect of titin-based passive tension on the length-dependence of activation (LDA) was studied by measuring the tension-pCa ..
  32. Trinick J, Tskhovrebova L. Titin: a molecular control freak. Trends Cell Biol. 1999;9:377-80 pubmed
    Recent studies of the giant protein titin have shed light on its roles in muscle assembly and elasticity and include the surprising findings described here...
  33. Fougerousse F, Bullen P, Herasse M, Lindsay S, Richard I, Wilson D, et al. Human-mouse differences in the embryonic expression patterns of developmental control genes and disease genes. Hum Mol Genet. 2000;9:165-73 pubmed
    ..Our study also shows how molecular analyses, while providing explanations for the observed differences, can be important in providing insights into mammalian evolution. ..
  34. Bellafiore M, Cappello F, Palumbo D, Macaluso F, Bianco A, Palma A, et al. Increased expression of titin in mouse gastrocnemius muscle in response to an endurance-training program. Eur J Histochem. 2007;51:119-24 pubmed
    b>Titin, a sarcomeric giant protein, plays crucial roles in muscle assembly, elasticity and stability. Little is known about titin adaptation to endurance exercise...
  35. Elhamine F, Radke M, Pfitzer G, Granzier H, Gotthardt M, Stehle R. Deletion of the titin N2B region accelerates myofibrillar force development but does not alter relaxation kinetics. J Cell Sci. 2014;127:3666-74 pubmed publisher
    Cardiac titin is the main determinant of sarcomere stiffness during diastolic relaxation...
  36. Buckle V, Guenet J, Simon Chazottes D, Love D, Davies K. Localisation of a dystrophin-related autosomal gene to 6q24 in man, and to mouse chromosome 10 in the region of the dystrophia muscularis (dy) locus. Hum Genet. 1990;85:324-6 pubmed
    ..A neuromuscular disease locus dystrophia muscularis (dy) has previously been assigned to this region of mouse chromosome 10. ..
  37. McKeown C, Nowak R, Gokhin D, Fowler V. Tropomyosin is required for cardiac morphogenesis, myofibril assembly, and formation of adherens junctions in the developing mouse embryo. Dev Dyn. 2014;243:800-17 pubmed publisher
    ..partner, tropomodulin1 (Tmod1), is also disorganized, and both myomesin-containing thick filaments as well as titin Z1Z2 fail to assemble in a striated pattern...
  38. Mohamed J, Lopez M, Cox G, Boriek A. Ankyrin repeat domain protein 2 and inhibitor of DNA binding 3 cooperatively inhibit myoblast differentiation by physical interaction. J Biol Chem. 2013;288:24560-8 pubmed publisher
    ..We demonstrate that the primary myoblasts of mdm (muscular dystrophy with myositis) mice (pMB(mdm)) overexpress ANKRD2 and ID3 (inhibitor of DNA binding 3) proteins ..
  39. Hamdani N, Krysiak J, Kreusser M, Neef S, dos Remedios C, Maier L, et al. Crucial role for Ca2(+)/calmodulin-dependent protein kinase-II in regulating diastolic stress of normal and failing hearts via titin phosphorylation. Circ Res. 2013;112:664-74 pubmed publisher
    Myocardial diastolic stiffness and cardiomyocyte passive force (F(passive)) depend in part on titin isoform composition and phosphorylation...
  40. Hutchinson K, Saripalli C, Chung C, Granzier H. Increased myocardial stiffness due to cardiac titin isoform switching in a mouse model of volume overload limits eccentric remodeling. J Mol Cell Cardiol. 2015;79:104-14 pubmed publisher
    ..biventricular hypertrophy; protein expression analysis in left ventricular (LV) tissue showed a marked decrease in titin's N2BA/N2B ratio with no change in phosphorylation of titin's spring region...
  41. Hidalgo C, Chung C, Saripalli C, Methawasin M, Hutchinson K, Tsaprailis G, et al. The multifunctional Ca(2+)/calmodulin-dependent protein kinase II delta (CaMKII?) phosphorylates cardiac titin's spring elements. J Mol Cell Cardiol. 2013;54:90-7 pubmed publisher
    b>Titin-based passive stiffness is post-translationally regulated by several kinases that phosphorylate specific spring elements located within titin's elastic I-band region...
  42. Herasse M, Ono Y, Fougerousse F, Kimura E, Stockholm D, Beley C, et al. Expression and functional characteristics of calpain 3 isoforms generated through tissue-specific transcriptional and posttranscriptional events. Mol Cell Biol. 1999;19:4047-55 pubmed
    ..In addition, expression of these isoforms seems to be regulated. Investigation of the proteolytic activities and titin binding abilities of the translation products of some of these isoforms clearly indicated that removal of these ..
  43. da Silva Lopes K, Pietas A, Radke M, Gotthardt M. Titin visualization in real time reveals an unexpected level of mobility within and between sarcomeres. J Cell Biol. 2011;193:785-98 pubmed publisher
    The giant muscle protein titin is an essential structural component of the sarcomere. It forms a continuous periodic backbone along the myofiber that provides resistance to mechanical strain...
  44. Smart N, Riegler J, Turtle C, Lygate C, McAndrew D, Gehmlich K, et al. Aberrant developmental titin splicing and dysregulated sarcomere length in Thymosin β4 knockout mice. J Mol Cell Cardiol. 2017;102:94-107 pubmed publisher
    ..Sarcomeric components, including titin, undergo an isoform transition to adjust ventricular filling...
  45. Hu B, Simon Keller K, Küffer S, Ströbel P, Braun T, Marx A, et al. Myf5 and Myogenin in the development of thymic myoid cells - Implications for a murine in vivo model of myasthenia gravis. Exp Neurol. 2016;277:76-85 pubmed publisher
    ..In combination with established immunization strategies (utilizing AChR or Titin), this model should enable us in the future testing the hypothesis that TMC play an indispensable role in the ..
  46. Schiaffino S, Reggiani C. Molecular diversity of myofibrillar proteins: gene regulation and functional significance. Physiol Rev. 1996;76:371-423 pubmed
    ..Additional isoforms, including products of tropomyosin, myosin light chain 1 fast, troponin T, titin, and nebulin genes, can be generated from the same gene through alternative splicing or use of alternative ..
  47. White J, Barro M, Makarenkova H, Sanger J, Sanger J. Localization of sarcomeric proteins during myofibril assembly in cultured mouse primary skeletal myotubes. Anat Rec (Hoboken). 2014;297:1571-84 pubmed publisher
    ..The data presented in this study on cultures of primary mouse skeletal myocytes are consistent with the premyofibril model of myofibrillogenesis previously proposed for both avian cardiac and skeletal muscle cells. ..
  48. Bogomolovas J, Gasch A, Simkovic F, Rigden D, Labeit S, Mayans O. Titin kinase is an inactive pseudokinase scaffold that supports MuRF1 recruitment to the sarcomeric M-line. Open Biol. 2014;4:140041 pubmed publisher
    ..This process involves the myofilament titin and, specifically, its kinase domain (TK; titin kinase) that translates mechanical signals into regulatory ..
  49. Granzier H, Radke M, Royal J, Wu Y, Irving T, Gotthardt M, et al. Functional genomics of chicken, mouse, and human titin supports splice diversity as an important mechanism for regulating biomechanics of striated muscle. Am J Physiol Regul Integr Comp Physiol. 2007;293:R557-67 pubmed
    b>Titin is a giant filamentous elastic protein that spans from the Z-disk to M-band regions of the sarcomere. The I-band region of titin is extensible and develops passive force in stretched sarcomeres...
  50. Cadar A, Zhong L, Lin A, Valenzuela M, Lim C. Upstream open reading frame in 5'-untranslated region reduces titin mRNA translational efficiency. Biochem Biophys Res Commun. 2014;453:185-91 pubmed publisher
    b>Titin is the largest known protein and a critical determinant of myofibril elasticity and sarcomere structure in striated muscle...
  51. Ye J, Beetz N, O Keeffe S, Tapia J, Macpherson L, Chen W, et al. hnRNP U protein is required for normal pre-mRNA splicing and postnatal heart development and function. Proc Natl Acad Sci U S A. 2015;112:E3020-9 pubmed publisher
    ..splicing of pre-mRNAs encoding proteins known to be critical for normal heart development and function, including Titin and calcium/calmodulin-dependent protein kinase II delta (Camk2d)...
  52. Buck D, Smith J, Chung C, Ono Y, Sorimachi H, Labeit S, et al. Removal of immunoglobulin-like domains from titin's spring segment alters titin splicing in mouse skeletal muscle and causes myopathy. J Gen Physiol. 2014;143:215-30 pubmed publisher
    b>Titin is a molecular spring that determines the passive stiffness of muscle cells. Changes in titin's stiffness occur in various myopathies, but whether these are a cause or an effect of the disease is unknown...
  53. Lin X, Miller J, Mankodi A, Kanadia R, Yuan Y, Moxley R, et al. Failure of MBNL1-dependent post-natal splicing transitions in myotonic dystrophy. Hum Mol Genet. 2006;15:2087-97 pubmed
    ..Sequestration of MBNL1, and failure to maintain these splicing transitions, has a pivotal role in the pathogenesis of muscle disease in DM. ..
  54. Anderson B, Bogomolovas J, Labeit S, Granzier H. Single molecule force spectroscopy on titin implicates immunoglobulin domain stability as a cardiac disease mechanism. J Biol Chem. 2013;288:5303-15 pubmed publisher
    b>Titin plays crucial roles in sarcomere organization and cardiac elasticity by acting as an intrasarcomeric molecular spring...
  55. Bennett P, Maggs A, Baines A, Pinder J. The transitional junction: a new functional subcellular domain at the intercalated disc. Mol Biol Cell. 2006;17:2091-100 pubmed
    ..intercalated disc thin filaments, identifiable by the presence of Z-disc proteins, alpha-actinin, and N-terminal titin. This allows for the usual elastic positioning of the A-band in the final sarcomere, whereas the transduction of ..
  56. Powers K, NISHIKAWA K, Joumaa V, Herzog W. Decreased force enhancement in skeletal muscle sarcomeres with a deletion in titin. J Exp Biol. 2016;219:1311-6 pubmed publisher
    ..This unexplained, enhanced force has been thought to originate in the giant protein titin, which becomes stiffer in actively compared with passively stretched sarcomeres by an unknown mechanism...
  57. Voelkel T, Andresen C, Unger A, Just S, Rottbauer W, Linke W. Lysine methyltransferase Smyd2 regulates Hsp90-mediated protection of the sarcomeric titin springs and cardiac function. Biochim Biophys Acta. 2013;1833:812-22 pubmed publisher
    ..the chaperone Hsp90, thus promoting the interaction of a Smyd2-methyl-Hsp90 complex with the N2A-domain of titin. This complex protects the sarcomeric I-band region and myocyte organization...
  58. Taylor Burt K, Monroy J, Pace C, Lindstedt S, Nishikawa K. Shiver me titin! Elucidating titin's role in shivering thermogenesis. J Exp Biol. 2015;218:694-702 pubmed publisher
    ..The link between shivering frequency and body mass may lie in the tuning of muscle elastic properties. Titin functions as a muscle 'spring', so shivering frequency may be linked to titin's structure...
  59. Perkin J, Slater R, Del Favero G, Lanzicher T, Hidalgo C, Anderson B, et al. Phosphorylating Titin's Cardiac N2B Element by ERK2 or CaMKIIδ Lowers the Single Molecule and Cardiac Muscle Force. Biophys J. 2015;109:2592-601 pubmed publisher
    b>Titin is a large filamentous protein that is responsible for the passive force of the cardiac sarcomere. Titin's force is generated by its I-band region, which includes the cardiac-specific N2B element...
  60. Müller Seitz M, Kaupmann K, Labeit S, Jockusch H. Chromosomal localization of the mouse titin gene and its relation to "muscular dystrophy with myositis" and nebulin genes on chromosome 2. Genomics. 1993;18:559-61 pubmed
    In the mouse, the genes for the structural components of the myofibril titin and nebulin, Ttn and Neb, map to proximal Chr 2, as does the gene for a muscle disease, "muscular dystrophy with myositis," mdm...
  61. Fritz J, Wolff J, Greaser M. Characterization of a partial cDNA clone encoding porcine skeletal muscle titin: comparison with rabbit and mouse skeletal muscle titin sequences. Comp Biochem Physiol B. 1993;105:357-60 pubmed
    1. A cDNA fragment encoding 571 amino acid residues of porcine skeletal muscle titin was isolated from total RNA using RNA-PCR. 2...
  62. Gautel M, Fürst D, Cocco A, Schiaffino S. Isoform transitions of the myosin binding protein C family in developing human and mouse muscles: lack of isoform transcomplementation in cardiac muscle. Circ Res. 1998;82:124-9 pubmed
    ..This suggests that transcomplementation of MyBP-C isoforms is possible in skeletal but not cardiac muscle. ..
  63. Huebsch K, Kudryashova E, Wooley C, Sher R, Seburn K, Spencer M, et al. Mdm muscular dystrophy: interactions with calpain 3 and a novel functional role for titin's N2A domain. Hum Mol Genet. 2005;14:2801-11 pubmed
    ..muscular dystrophy and limb-girdle muscular dystrophy 2J are caused by mutations in the giant sarcomeric protein titin (TTN) adjacent to a binding site for the muscle-specific protease calpain 3 (CAPN3)...
  64. Peng J, Raddatz K, Molkentin J, Wu Y, Labeit S, Granzier H, et al. Cardiac hypertrophy and reduced contractility in hearts deficient in the titin kinase region. Circulation. 2007;115:743-51 pubmed
    b>Titin is a giant protein crucial for the assembly and elasticity of the sarcomere. Recently, titin has been linked to signal transduction through its kinase domain, which has been proposed to sense mechanical load...
  65. Lee E, Peng J, Radke M, Gotthardt M, Granzier H. Calcium sensitivity and the Frank-Starling mechanism of the heart are increased in titin N2B region-deficient mice. J Mol Cell Cardiol. 2010;49:449-58 pubmed publisher
    Previous work suggests that titin-based passive tension is a factor in the Frank-Starling mechanism of the heart, by increasing length-dependent activation (LDA) through an increase in calcium sensitivity at long sarcomere length...
  66. Slater R, Strom J, Granzier H. Effect of exercise on passive myocardial stiffness in mice with diastolic dysfunction. J Mol Cell Cardiol. 2017;108:24-33 pubmed publisher
    ..In both genotypes, this reduction is due to an increase in the compliance of titin whereas ECM-based stiffness was unaffected...
  67. Tonino P, Kiss B, Strom J, Methawasin M, Smith J, Kolb J, et al. The giant protein titin regulates the length of the striated muscle thick filament. Nat Commun. 2017;8:1041 pubmed publisher
    ..It has been speculated that the mechanism by which thick filament length is controlled involves the giant protein titin, but no conclusive support for this hypothesis exists...
  68. Charton K, Sarparanta J, Vihola A, Milic A, Jonson P, Suel L, et al. CAPN3-mediated processing of C-terminal titin replaced by pathological cleavage in titinopathy. Hum Mol Genet. 2015;24:3718-31 pubmed publisher
    Mutations in the extreme C-terminus of titin (TTN), situated in the sarcomeric M-band, cause tibial muscular dystrophy (TMD) and limb-girdle muscular dystrophy 2J (LGMD2J)...
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    ..Given these results, we conclude that Tln1 and Tln2 have distinct functions in the myocardium. Our data show that reduction of CM Tln1 expression can lead to improved cardiac remodeling following pressure overload. ..
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    Titin (also known as connectin) is an intrasarcomeric muscle protein that functions as a molecular spring and generates passive tension upon muscle stretch...
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    ..In support of this, we demonstrated that the Z-disk proteins, ZASP, titin and vinculin preferentially bind to ?-actinin-2...
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