Genomes and Genes
Summary: Myosin type II isoforms found in cardiac muscle.
- Roncarati R, Latronico M, Musumeci B, Aurino S, Torella A, Bang M, et al. Unexpectedly low mutation rates in beta-myosin heavy chain and cardiac myosin binding protein genes in Italian patients with hypertrophic cardiomyopathy. J Cell Physiol. 2011;226:2894-900 pubmed publisher..This finding, coupled to the clinical diversity of our cohort, emphasizes the complexity of HCM and the need for more inclusive investigative approaches in order to fully understand the pathogenesis of this disease...
- Bell M, Buvoli M, Leinwand L. Uncoupling of expression of an intronic microRNA and its myosin host gene by exon skipping. Mol Cell Biol. 2010;30:1937-45 pubmed publisher..Thus, concerted transcription and alternative splicing uncouple the level of expression of MYH7b and miR-499 when their coexpression is not required. ..
- Walsh R, Rutland C, Thomas R, Loughna S. Cardiomyopathy: a systematic review of disease-causing mutations in myosin heavy chain 7 and their phenotypic manifestations. Cardiology. 2010;115:49-60 pubmed publisher..This study suggests that mutation location in the MYH7 gene and changes in amino acid composition can have a negative impact on the disease outcome in individuals with cardiomyopathy. ..
- Stalpers X, Verrips A, Braakhekke J, Lammens M, van den Wijngaard A, Mostert A. Scoliosis surgery in a patient with "de novo" myosin storage myopathy. Neuromuscul Disord. 2011;21:812-5 pubmed publisher..We describe a patient with this uncommon myopathy, caused by a new p.K1784delK mutation in the MYH7 gene. The patient developed a severe thoracolumbar scoliosis and had scoliosis surgery...
- Klaassen S, Probst S, Oechslin E, Gerull B, Krings G, Schuler P, et al. Mutations in sarcomere protein genes in left ventricular noncompaction. Circulation. 2008;117:2893-901 pubmed publisher..Our findings support the hypothesis that there is a shared molecular etiology of different cardiomyopathic phenotypes. ..
- Mathew S, Mascareno E, Siddiqui M. A ternary complex of transcription factors, Nishéd and NFATc4, and co-activator p300 bound to an intronic sequence, intronic regulatory element, is pivotal for the up-regulation of myosin light chain-2v gene in cardiac hypertrophy. J Biol Chem. 2004;279:41018-27 pubmed
- Malmqvist U, Aronshtam A, Lowey S. Cardiac myosin isoforms from different species have unique enzymatic and mechanical properties. Biochemistry. 2004;43:15058-65 pubmed..Thus, nature has adapted the function of cardiac myosin isoforms to optimize power output for hearts of a given species. ..
- Meder B, Haas J, Keller A, Heid C, Just S, Borries A, et al. Targeted next-generation sequencing for the molecular genetic diagnostics of cardiomyopathies. Circ Cardiovasc Genet. 2011;4:110-22 pubmed publisher..The approach presented here allows for the first time a comprehensive genetic screening in patients with hereditary DCM or HCM in a fast and cost-efficient manner. ..
- Revera M, van der Merwe L, Heradien M, Goosen A, Corfield V, Brink P, et al. Troponin T and beta-myosin mutations have distinct cardiac functional effects in hypertrophic cardiomyopathy patients without hypertrophy. Cardiovasc Res. 2008;77:687-94 pubmed
- Petersen J, Felker G. Inotropes in the management of acute heart failure. Crit Care Med. 2008;36:S106-11 pubmed publisher..Whether newer inotropes with differing mechanisms of action will realize the potential clinical benefits of inotropic therapy without the risk remains a subject of ongoing investigation. ..
- Hershberger R, Norton N, Morales A, Li D, Siegfried J, Gonzalez Quintana J. Coding sequence rare variants identified in MYBPC3, MYH6, TPM1, TNNC1, and TNNI3 from 312 patients with familial or idiopathic dilated cardiomyopathy. Circ Cardiovasc Genet. 2010;3:155-61 pubmed publisher..Rare variants in these 5 genes likely or possibly caused 10.6% of DCM in this cohort. When combined with our prior resequencing reports, approximately 27% of DCM probands had possible or likely disease-causing variants identified. ..
- Ching Y, Ghosh T, Cross S, Packham E, Honeyman L, Loughna S, et al. Mutation in myosin heavy chain 6 causes atrial septal defect. Nat Genet. 2005;37:423-8 pubmed..These data provide evidence for a link between a transcription factor, a structural protein and congenital heart disease. ..
- Gilles L, Bluteau D, Boukour S, Chang Y, Zhang Y, Robert T, et al. MAL/SRF complex is involved in platelet formation and megakaryocyte migration by regulating MYL9 (MLC2) and MMP9. Blood. 2009;114:4221-32 pubmed publisher..Finally, the use of a shRNA to decrease MYL9 expression showed that MYL9 was involved in proplatelet formation. MAL/SRF complex is thus involved in platelet formation and megakaryocyte migration by regulating MYL9 and MMP9. ..
- Granados Riveron J, Ghosh T, Pope M, Bu Lock F, Thornborough C, Eason J, et al. Alpha-cardiac myosin heavy chain (MYH6) mutations affecting myofibril formation are associated with congenital heart defects. Hum Mol Genet. 2010;19:4007-16 pubmed publisher..Our data indicate that functional variants of MYH6 are associated with cardiac malformations in addition to ASD and provide a novel potential mechanism. Such phenotypic heterogeneity has been observed in other genes mutated in CHD. ..
- Latinkic B, Cooper B, Smith S, Kotecha S, Towers N, Sparrow D, et al. Transcriptional regulation of the cardiac-specific MLC2 gene during Xenopus embryonic development. Development. 2004;131:669-79 pubmed
- Sturge J, Wienke D, Isacke C. Endosomes generate localized Rho-ROCK-MLC2-based contractile signals via Endo180 to promote adhesion disassembly. J Cell Biol. 2006;175:337-47 pubmed..We propose migration driven by Endo180 as a model for the spatial regulation of contractility and adhesion dynamics by endosomes. ..
- Hougs L, Havndrup O, Bundgaard H, Køber L, Vuust J, Larsen L, et al. One third of Danish hypertrophic cardiomyopathy patients with MYH7 mutations have mutations [corrected] in MYH7 rod region. Eur J Hum Genet. 2005;13:161-5 pubmed
- Sommese R, Sung J, Nag S, Sutton S, Deacon J, Choe E, et al. Molecular consequences of the R453C hypertrophic cardiomyopathy mutation on human ?-cardiac myosin motor function. Proc Natl Acad Sci U S A. 2013;110:12607-12 pubmed publisher..Loaded in vitro motility assay confirms that the net force in the ensemble is indeed increased. Overall, this study suggests that the R453C mutation should result in a hypercontractile state in the heart muscle. ..
- Buvoli M, Hamady M, Leinwand L, Knight R. Bioinformatics assessment of beta-myosin mutations reveals myosin's high sensitivity to mutations. Trends Cardiovasc Med. 2008;18:141-9 pubmed publisher..Increasing knowledge of the characteristics of MH7 mutations may provide a valuable resource for scientists and clinicians studying diagnosis, risk stratification, and treatment of disease associated with these mutations. ..
- Munkvik M, Lunde P, Aronsen J, Birkeland J, Sjaastad I, Sejersted O. Attenuated fatigue in slow twitch skeletal muscle during isotonic exercise in rats with chronic heart failure. PLoS ONE. 2011;6:e22695 pubmed publisher..This observation is in striking contrast to previous reports which have employed isometric contractions to induce fatigue. ..
- Munkvik M, Lunde P, Sejersted O. Causes of fatigue in slow-twitch rat skeletal muscle during dynamic activity. Am J Physiol Regul Integr Comp Physiol. 2009;297:R900-10 pubmed publisher..Although metabolic changes may account for the changes of F(max), -dF/dt, and V(0), dephosphorylation of MLC2s may be involved in the fatigue seen as sustained slower contraction velocities and decreased muscle shortening...
- Sardao V, Oliveira P, Holy J, Oliveira C, Wallace K. Morphological alterations induced by doxorubicin on H9c2 myoblasts: nuclear, mitochondrial, and cytoskeletal targets. Cell Biol Toxicol. 2009;25:227-43 pubmed publisher..The results obtained also provide new and previously unknown targets that can contribute to understand the mechanisms involved in the cardiotoxicity of Dox. ..
- Li R, Martin M, Liu Y, Wang B, Patel R, Zhu J, et al. Fragment-based and structure-guided discovery and optimization of Rho kinase inhibitors. J Med Chem. 2012;55:2474-8 pubmed publisher..Compounds 18 and 24 inhibited potently the phosphorylation of the ROCK substrate MLC2 in intact human breast cancer cells. ..
- Iascone M, Marchetti D, Ferrazzi P. Gene symbol: MYH7. Hum Genet. 2007;120:916 pubmed
- Andersen P, Havndrup O, Hougs L, Sørensen K, Jensen M, Larsen L, et al. Diagnostic yield, interpretation, and clinical utility of mutation screening of sarcomere encoding genes in Danish hypertrophic cardiomyopathy patients and relatives. Hum Mutat. 2009;30:363-70 pubmed publisher..Mutation-screening was superior to clinical investigation in identification of individuals not at increased risk, where follow-up is redundant, but should be offered in all families with relatives at risk for developing HCM. ..
- van der Velden J, Papp Z, Boontje N, Zaremba R, de Jong J, Janssen P, et al. The effect of myosin light chain 2 dephosphorylation on Ca2+ -sensitivity of force is enhanced in failing human hearts. Cardiovasc Res. 2003;57:505-14 pubmed
- van der Velden J, Papp Z, Zaremba R, Boontje N, de Jong J, Owen V, et al. Increased Ca2+-sensitivity of the contractile apparatus in end-stage human heart failure results from altered phosphorylation of contractile proteins. Cardiovasc Res. 2003;57:37-47 pubmed
- Haase D, Lehmann M, Körner M, Korfer R, Sigusch H, Figulla H. Identification and validation of selective upregulation of ventricular myosin light chain type 2 mRNA in idiopathic dilated cardiomyopathy. Eur J Heart Fail. 2002;4:23-31 pubmed..we have demonstrated that SSH is a useful method to identify differential myocardial upregulation of genes. Upregulation of MLC2V can be judged as a specific IDCM related feature, which might be clinically helpful. ..
- Zagorska A, Deak M, Campbell D, Banerjee S, Hirano M, Aizawa S, et al. New roles for the LKB1-NUAK pathway in controlling myosin phosphatase complexes and cell adhesion. Sci Signal. 2010;3:ra25 pubmed publisher..Thus, LKB1 can influence the phosphorylation of targets not only through the AMPK family of kinases but also by controlling phosphatase complexes. ..
- Dellefave L, Pytel P, Mewborn S, Mora B, Guris D, Fedson S, et al. Sarcomere mutations in cardiomyopathy with left ventricular hypertrabeculation. Circ Cardiovasc Genet. 2009;2:442-9 pubmed publisher..Genetic testing should be considered for cardiomyopathy with hypertrabeculation. ..
- Petzhold D, Lossie J, Keller S, Werner S, Haase H, Morano I. Human essential myosin light chain isoforms revealed distinct myosin binding, sarcomeric sorting, and inotropic activity. Cardiovasc Res. 2011;90:513-20 pubmed publisher..Intense myosin binding of hALC-1 provides a mechanism for preferential sarcomeric sorting and Ca(2+)-independent positive inotropic activity. ..
- Fousteri G, Dave A, Morin B, Omid S, Croft M, Von Herrath M. Nasal cardiac myosin peptide treatment and OX40 blockade protect mice from acute and chronic virally-induced myocarditis. J Autoimmun. 2011;36:210-20 pubmed publisher..Altogether, these results chart the way for novel prevention and intervention strategies for viral myocarditis. ..
- Crilley J, Boehm E, Blair E, Rajagopalan B, Blamire A, Styles P, et al. Hypertrophic cardiomyopathy due to sarcomeric gene mutations is characterized by impaired energy metabolism irrespective of the degree of hypertrophy. J Am Coll Cardiol. 2003;41:1776-82 pubmed..The presence of energetic abnormalities, even in those without hypertrophy, supports a proposed link between altered cardiac energetics and development of the disease phenotype. ..
- Mohun T, Latinkic B, Towers N, Kotecha S. Regulation of cardiac muscle differentiation in Xenopus laevis embryos. Cold Spring Harb Symp Quant Biol. 2002;67:13-8 pubmed
- Jacques A, Briceno N, Messer A, Gallon C, Jalilzadeh S, Garcia E, et al. The molecular phenotype of human cardiac myosin associated with hypertrophic obstructive cardiomyopathy. Cardiovasc Res. 2008;79:481-91 pubmed publisher..The presence of a myosin heavy chain mutation causing hypertrophic cardiomyopathy can be predicted from a simple functional assay. ..
- Darin N, Tajsharghi H, Ostman Smith I, Gilljam T, Oldfors A. New skeletal myopathy and cardiomyopathy associated with a missense mutation in MYH7. Neurology. 2007;68:2041-2 pubmed
- Wang Y, Burghardt T. InÂ vitro actin motility velocity varies linearly with the number of myosin impellers. Arch Biochem Biophys. 2017;618:1-8 pubmed publisher..Variable step-size characteristics imply cardiac myosin maintains a velocity dynamic range not involving strain. ..
- Iwai L, Juliano M, Juliano L, Kalil J, Cunha Neto E. T-cell molecular mimicry in Chagas disease: identification and partial structural analysis of multiple cross-reactive epitopes between Trypanosoma cruzi B13 and cardiac myosin heavy chain. J Autoimmun. 2005;24:111-7 pubmed
- Chang A, Mahajan P, Knapp S, Barton H, Sweeney H, Kamm K, et al. Cardiac myosin light chain is phosphorylated by Ca2+/calmodulin-dependent and -independent kinase activities. Proc Natl Acad Sci U S A. 2016;113:E3824-33 pubmed publisher..Thus, RLC phosphorylation in cardiac muscle may be regulated by two different protein kinases with distinct biochemical regulatory properties. ..
- Tarigopula M, Davis R, Mungai P, Ryba D, Wieczorek D, Cowan C, et al. Cardiac myosin light chain phosphorylation and inotropic effects of a biased ligand, TRV120023, in a dilated cardiomyopathy model. Cardiovasc Res. 2015;107:226-34 pubmed publisher..AT1R biased ligands may prove to be a novel inotropic approach in familial DCM. ..
- Hashem S, Tiberti M, Fornili A. Allosteric modulation of cardiac myosin dynamics by omecamtiv mecarbil. PLoS Comput Biol. 2017;13:e1005826 pubmed publisher..The location of the residues responsible for these effects suggests possible strategies for the future development of improved drugs and the targeting of specific cardiomyopathy-related mutations...
- Garg V, Frishman W. A new approach to inotropic therapy in the treatment of heart failure: cardiac myosin activators in treatment of HF. Cardiol Rev. 2013;21:155-9 pubmed publisher..Cardiac myosin activators show great promise and may prove to be a safer and more effective therapeutic approach for the treatment of systolic heart failure. ..
- Wang H, ZOU Y, Song L, WANG J, Sun K, Song X, et al. [The genotype-phenotype correlation of the MYH7 gene c.1273G > a mutation in familial hypertrophic cardiomyopathy]. Yi Chuan. 2009;31:485-8 pubmed..The c.1273G>A mutation of the MYH7 gene might be the causal mutation of the familial HCM. The heterogeneity of phenotypes suggested that multiple factors may be involved in the pathogenesis of HCM. ..
- El Menyar A, Almahmeed W. Heart failure in 2010. Expert Rev Cardiovasc Ther. 2010;8:1231-4 pubmed publisher..The congress highlighted new drugs, novel biomarkers, updated trials, the role of imaging in risk stratification and the importance of telecare in the reduction of heart failure readmission. ..
- Kulikovskaya I, McClellan G, Levine R, Winegrad S. Multiple forms of cardiac myosin-binding protein C exist and can regulate thick filament stability. J Gen Physiol. 2007;129:419-28 pubmed..We hypothesize that modulation of filament stability can be coupled at the molecular level with the strength of contraction by the sensitivity of each to the concentration of calcium ions...
- Verma D, Levchenko T, Bernstein E, Mongayt D, Torchilin V. ATP-loaded immunoliposomes specific for cardiac myosin provide improved protection of the mechanical functions of myocardium from global ischemia in an isolated rat heart model. J Drug Target. 2006;14:273-80 pubmed..The extent of preservation depended on the amount of the antibody present on the surface of the ATP-IL. ..
- Moss R, Fitzsimons D. Myosin light chain 2 into the mainstream of cardiac development and contractility. Circ Res. 2006;99:225-7 pubmed
- Muelas N, Hackman P, Luque H, Garces Sanchez M, Azorin I, Suominen T, et al. MYH7 gene tail mutation causing myopathic profiles beyond Laing distal myopathy. Neurology. 2010;75:732-41 pubmed publisher..Mutations in genes encoding other sarcomeric and reticulo-sarcoplasmic proteins involved in calcium regulation share pathologic characteristics with our patients, suggesting a possible pathogenetic connection. ..
- Navarro López F. [Hypertrophic cardiomyopathy: never-ending complexity]. Rev Esp Cardiol. 2006;59:994-6 pubmed