connectin

Summary

Summary: A giant elastic protein of molecular mass ranging from 2,993 kDa (cardiac), 3,300 kDa (psoas), to 3,700 kDa (soleus) having a kinase domain. The amino- terminal is involved in a Z line binding, and the carboxy-terminal region is bound to the myosin filament with an overlap between the counter-connectin filaments at the M line.

Top Publications

  1. Kanda K, Sakuma J, Akimoto T, Kawakami Y, Suzuki K. Detection of titin fragments in urine in response to exercise-induced muscle damage. PLoS ONE. 2017;12:e0181623 pubmed publisher
    ..a calf-raise exercise, including repetitive eccentric muscle contractions, and found that a titin (also known as connectin) N-terminal fragment molecule appears in the urine after eccentric exercise...
  2. González Morales N, Holenka T, Schock F. Filamin actin-binding and titin-binding fulfill distinct functions in Z-disc cohesion. PLoS Genet. 2017;13:e1006880 pubmed publisher
    ..Thus, Z-discs require filamin to withstand the strong contractile forces acting on them. ..
  3. Tskhovrebova L, Trinick J, Sleep J, Simmons R. Elasticity and unfolding of single molecules of the giant muscle protein titin. Nature. 1997;387:308-12 pubmed
    The giant muscle protein titin, also called connectin, is responsible for the elasticity of relaxed striated muscle, as well as acting as the molecular scaffold for thick-filament formation...
  4. Kötter S, Andresen C, Kruger M. Titin: central player of hypertrophic signaling and sarcomeric protein quality control. Biol Chem. 2014;395:1341-52 pubmed publisher
    ..This review focuses on the emerging role of titin in mechanosensing and hypertrophic signaling, and further highlights recent evidence that links titin to sarcomeric protein turnover. ..
  5. LeWinter M, Granzier H. Titin is a major human disease gene. Circulation. 2013;127:938-44 pubmed publisher
  6. Saide J, Chin Bow S, Hogan Sheldon J, Busquets Turner L. Z-band proteins in the flight muscle and leg muscle of the honeybee. J Muscle Res Cell Motil. 1990;11:125-36 pubmed
    ..Surprisingly, however, mAb P binds within the A-bands of synchronous fibres, not between the A- and Z-bands as in asynchronous fibrillar muscle. ..
  7. Tan H, Su W, Wang P, Zhang W, Sattler M, Zou P. Expression and purification of a difficult sarcomeric protein: Telethonin. Protein Expr Purif. 2017;140:74-80 pubmed publisher
    ..Expression of this fusion protein, named ZTZ, affords high yields of soluble expressed and purified protein. ..
  8. LeWinter M, Granzier H. Cardiac titin: a multifunctional giant. Circulation. 2010;121:2137-45 pubmed publisher
  9. Sutko J, Publicover N, Moss R. Titin: an elastic link between length and active force production in myocardium. Circulation. 2001;104:1585-7 pubmed

More Information

Publications31

  1. Munoz V, Serrano L. Elucidating the folding problem of helical peptides using empirical parameters. III. Temperature and pH dependence. J Mol Biol. 1995;245:297-308 pubmed
    ..The inclusion of these terms allow us to calculate the helical behaviour of polyalanine-based peptides, as well as of complex natural sequences, under different experimental conditions. ..
  2. Marx A, Osborn M, Tzartos S, Geuder K, Schalke B, Nix W, et al. A striational muscle antigen and myasthenia gravis-associated thymomas share an acetylcholine-receptor epitope. Dev Immunol. 1992;2:77-84 pubmed
  3. Tskhovrebova L, Bennett P, Gautel M, Trinick J. Titin ruler hypothesis not refuted. Proc Natl Acad Sci U S A. 2015;112:E1172 pubmed publisher
  4. Tschope C, Van Linthout S, Spillmann F, Klein O, Biewener S, Remppis A, et al. Cardiac contractility modulation signals improve exercise intolerance and maladaptive regulation of cardiac key proteins for systolic and diastolic function in HFpEF. Int J Cardiol. 2016;203:1061-6 pubmed publisher
  5. Golenhofen N, Htun P, Ness W, Koob R, Schaper W, Drenckhahn D. Binding of the stress protein alpha B-crystallin to cardiac myofibrils correlates with the degree of myocardial damage during ischemia/reperfusion in vivo. J Mol Cell Cardiol. 1999;31:569-80 pubmed
    ..Ischemia-induced myofibrillar targeting of alpha B-crystallin probably requires additional structural and posttranslational modifications of myofibrillar components in juxtaposition to I-bands. ..
  6. Watanabe O, Maruyama I, Arimura K, Kitajima I, Arimura H, Hanatani M, et al. Overproduction of vascular endothelial growth factor/vascular permeability factor is causative in Crow-Fukase (POEMS) syndrome. Muscle Nerve. 1998;21:1390-7 pubmed
    ..The principal isoform of VEGF in Crow-Fukase syndrome was VEGF165. Elevated VEGF was independent of M-protein. Our results suggest that the overproduction of VEGF is important in the pathogenesis of this disorder...
  7. Becher P, Jugdutt B, Baugh J, Schmack B. Experimental Heart Failure Models and Their Pathophysiological Characterization. Biomed Res Int. 2016;2016:2538263 pubmed publisher
  8. Mademont Soler I, Mates J, Yotti R, Espinosa M, Pérez Serra A, Fernandez Avila A, et al. Additional value of screening for minor genes and copy number variants in hypertrophic cardiomyopathy. PLoS ONE. 2017;12:e0181465 pubmed publisher
  9. Heidlauf T, Klotz T, Rode C, Siebert T, Röhrle O. A continuum-mechanical skeletal muscle model including actin-titin interaction predicts stable contractions on the descending limb of the force-length relation. PLoS Comput Biol. 2017;13:e1005773 pubmed publisher
    ..This could be a key to durable functioning of the muscle because large local stretches, that might harm, for example, the transverse-tubule system, are avoided...
  10. Zhang C, Zhang H, Wu G, Luo X, Zhang C, Zou Y, et al. Titin-Truncating Variants Increase the Risk of Cardiovascular Death in Patients With Hypertrophic Cardiomyopathy. Can J Cardiol. 2017;33:1292-1297 pubmed publisher
    ..6%]) [adjusted hazard ratio, 6.88; 95% confidence interval, 2.04-23.20; P = 0.002). Our study suggests that TTNtv might be a genetic modifier of HCM and confer an increased risk for cardiovascular death. ..
  11. Linke W, Ivemeyer M, Olivieri N, Kolmerer B, Ruegg J, Labeit S. Towards a molecular understanding of the elasticity of titin. J Mol Biol. 1996;261:62-71 pubmed
    ..when stretched and this property is thought to reside primarily within the giant filamentous protein, titin (connectin)...
  12. Mendes de Almeida R, Tavares J, Martins S, Carvalho T, Enguita F, Brito D, et al. Whole gene sequencing identifies deep-intronic variants with potential functional impact in patients with hypertrophic cardiomyopathy. PLoS ONE. 2017;12:e0182946 pubmed publisher
    ..Our data suggest that deep intronic variation contributes to HCM phenotype. ..
  13. Suktitipat B, Sathirareuangchai S, Roothumnong E, Thongnoppakhun W, Wangkiratikant P, Vorasan N, et al. Molecular investigation by whole exome sequencing revealed a high proportion of pathogenic variants among Thai victims of sudden unexpected death syndrome. PLoS ONE. 2017;12:e0180056 pubmed publisher
    ..WES can help to identify the genetic causes in victims of SUDS and may help to further guide investigations into their relatives to prevent additional SUDS victims. ..
  14. König E, Volpato C, Motta B, Blankenburg H, Picard A, Pramstaller P, et al. Exploring digenic inheritance in arrhythmogenic cardiomyopathy. BMC Med Genet. 2017;18:145 pubmed publisher
    ..In this study we report genes that might act as digenic players in ACM pathogenesis, on the basis of co-segregation with PKP2 mutations. Validation in larger cohorts is still required to prove the utility of this model. ..
  15. Koskinen S, Kyrolainen H, Flink R, Selänne H, Gagnon S, Ahtiainen J, et al. Human skeletal muscle type 1 fibre distribution and response of stress-sensing proteins along the titin molecule after submaximal exhaustive exercise. Histochem Cell Biol. 2017;148:545-555 pubmed publisher
    ..Activation of these proteins represents an initial step forward adaptive remodelling of the exercised muscle and may also be involved in the initiation of myofibre repair. ..
  16. Manteca A, Schönfelder J, Alonso Caballero A, Fertin M, Barruetabeña N, Faria B, et al. Mechanochemical evolution of the giant muscle protein titin as inferred from resurrected proteins. Nat Struct Mol Biol. 2017;24:652-657 pubmed publisher
    ..We hypothesize that mechanical adjustments in titin contributed to physiological changes that allowed the muscular development and diversity of modern tetrapods. ..
  17. Manteca A, Alonso Caballero A, Fertin M, Poly S, De Sancho D, Perez Jimenez R. The influence of disulfide bonds on the mechanical stability of proteins is context dependent. J Biol Chem. 2017;292:13374-13380 pubmed publisher
  18. Hastings R, de Villiers C, Hooper C, Ormondroyd L, Pagnamenta A, Lise S, et al. Combination of Whole Genome Sequencing, Linkage, and Functional Studies Implicates a Missense Mutation in Titin as a Cause of Autosomal Dominant Cardiomyopathy With Features of Left Ventricular Noncompaction. Circ Cardiovasc Genet. 2016;9:426-435 pubmed
    ..It furthermore highlights that rare titin missense variants, currently often ignored or left uninterpreted, should be considered to be relevant for cardiomyopathies and can be identified by the approach presented here. ..
  19. Yang C, Yu T, Han C, Qin W, Liao X, Yu L, et al. Genome-Wide Association Study of MKI67 Expression and its Clinical Implications in HBV-Related Hepatocellular Carcinoma in Southern China. Cell Physiol Biochem. 2017;42:1342-1357 pubmed publisher
    ..Variants near TTN and CCDC8 were associated with MKI67 expression, and rs2288563 and rs2562832 in TTN are potential biomarkers for the prediction of clinical outcomes in HBV-related HCC patients. ..
  20. Rassier D. Sarcomere mechanics in striated muscles: from molecules to sarcomeres to cells. Am J Physiol Cell Physiol. 2017;313:C134-C145 pubmed publisher
    ..A common mechanism associated with sarcomere and half-sarcomere length nonuniformities and a Ca2+-induced increase in the stiffness of titin is proposed to explain observations that derive from these studies. ..
  21. Tayal U, Newsome S, Buchan R, Whiffin N, Halliday B, Lota A, et al. Phenotype and Clinical Outcomes of Titin Cardiomyopathy. J Am Coll Cardiol. 2017;70:2264-2274 pubmed publisher
  22. Zhu C, Yin Z, Ren J, McCormick R, Ford S, Guo W. RBM20 is an essential factor for thyroid hormone-regulated titin isoform transition. J Mol Cell Biol. 2015;7:88-90 pubmed publisher