Nebulin and titin modulate cross-bridge cycling and length-dependent calcium sensitivity

Mijailovich, Srboljub M.; Stojanovic, Boban; Nedic, Djordje; Svicevic, Marina; Geeves, Michael A.; Irving, Thomas C.; Granzier, Henk L.

doi:10.1085/jgp.201812165

Title: Nebulin and titin modulate cross-bridge cycling and length-dependent calcium sensitivity

Journal Article · Thu Apr 04 00:00:00 EDT 2019 · Journal of General Physiology

DOI:https://doi.org/10.1085/jgp.201812165· OSTI ID:1558308

^[1];

^[2]; Nedic, Djordje ^[2]; Svicevic, Marina ^[2];

^[3];

^[4];

^[5]

Northeastern Univ., Boston, MA (United States); Illinois Inst. of Technology, Chicago, IL (United States)
Univ. of Kragujevac (Serbia)
Univ. of Kent (United Kingdom)
Illinois Inst. of Technology, Chicago, IL (United States)
Univ. of Arizona, Tucson, AZ (United States)

Various mutations in the structural proteins nebulin and titin that are present in human disease are known to affect the contractility of striated muscle. Loss of nebulin is associated with reduced actin filament length and impairment of myosin binding to actin, whereas titin is thought to regulate muscle passive elasticity and is likely involved in length-dependent activation. Here, we sought to assess the modulation of muscle function by these sarcomeric proteins by using the computational platform muscle simulation code (MUSICO) to quantitatively separate the effects of structural changes, kinetics of cross-bridge cycling, and calcium sensitivity of the thin filaments. The simulations show that variation in thin filament length cannot by itself account for experimental observations of the contractility in nebulin-deficient muscle, but instead must be accompanied by a decreased myosin binding rate. Additionally, to match the observed calcium sensitivity, the rate of TnI detachment from actin needed to be increased. Simulations for cardiac muscle provided quantitative estimates of the effects of different titin-based passive elasticities on muscle force and activation in response to changes in sarcomere length and interfilament lattice spacing. Predicted force–pCa relations showed a decrease in both active tension and sensitivity to calcium with a decrease in passive tension and sarcomere length. We conclude that this behavior is caused by partial redistribution of the muscle load between active muscle force and titin-dependent passive force, and also by redistribution of stretch along the thin filament, which together modulate the release of TnI from actin. These data help advance understanding of how nebulin and titin mutations affect muscle function.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH); British Heart Foundation; European Research Council (ERC); Serbian Ministry of Science

Grant/Contract Number:: R01 AR048776; P41 GM103622; R35HL144998; R01AR053897; III41007; OI174028; R01 DC 011528

OSTI ID:: 1558308

Journal Information:: Journal of General Physiology, Vol. 151, Issue 5; ISSN 0022-1295

Publisher:: Rockefeller University PressCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

Citation Metrics:

Cited by: 22 works

Citation information provided by
Web of Science

References (130)

Mechanical properties of tropomyosin and implications for muscle regulation Phillips, George N.; Chacko, Susan Biopolymers, Vol. 38, Issue 1 https://doi.org/10.1002/(SICI)1097-0282(199601)38:1%3C89::AID-BIP7%3E3.0.CO;2-S	journal	January 1996
Computational simulation of hypertrophic cardiomyopathy mutations in Troponin I: Influence of increased myofilament calcium sensitivity on isometric force, ATPase and [Ca2+]i Kataoka, Aya; Hemmer, Carolyn; Chase, P. Bryant Journal of Biomechanics, Vol. 40, Issue 9 https://doi.org/10.1016/j.jbiomech.2006.09.026	journal	January 2007
Shortening of the Elastic Tandem Immunoglobulin Segment of Titin Leads to Diastolic Dysfunction Chung, Charles S.; Hutchinson, Kirk R.; Methawasin, Mei Circulation, Vol. 128, Issue 1 https://doi.org/10.1161/CIRCULATIONAHA.112.001268	journal	July 2013
The force exerted by a single kinesin molecule against a viscous load Hunt, A. J.; Gittes, F.; Howard, J. Biophysical Journal, Vol. 67, Issue 2 https://doi.org/10.1016/S0006-3495(94)80537-5	journal	August 1994
The Sarcomeric Protein Nebulin: Another Multifunctional Giant in Charge of Muscle Strength Optimization Ottenheijm, Coen A. C.; Granzier, Henk; Labeit, Siegfried Frontiers in Physiology, Vol. 3 https://doi.org/10.3389/fphys.2012.00037	journal	January 2012
A Spatially Explicit Nanomechanical Model of the Half-Sarcomere: Myofilament Compliance Affects Ca ²⁺ -Activation Chase, P. Bryant; Macpherson, J. Michael; Daniel, Thomas L. Annals of Biomedical Engineering, Vol. 32, Issue 11 https://doi.org/10.1114/B:ABME.0000049039.89173.08	journal	November 2004
Thin filament length in the cardiac sarcomere varies with sarcomere length but is independent of titin and nebulin Kolb, Justin; Li, Frank; Methawasin, Mei Journal of Molecular and Cellular Cardiology, Vol. 97 https://doi.org/10.1016/j.yjmcc.2016.04.013	journal	August 2016
X-ray diffraction from striated muscles and nerves in normal and dystrophic mice Kurg, Teorin; Stinson, Robert H.; Millman, Barry M. Muscle & Nerve, Vol. 5, Issue 3 https://doi.org/10.1002/mus.880050311	journal	March 1982
Titin/connectin-based modulation of the Frank-Starling mechanism of the heart Fukuda, Norio; Granzier, Henk L. Journal of Muscle Research and Cell Motility, Vol. 26, Issue 6-8 https://doi.org/10.1007/s10974-005-9038-1	journal	February 2006
Dilated cardiomyopathy myosin mutants have reduced force-generating capacity Ujfalusi, Zoltan; Vera, Carlos D.; Mijailovich, Srbolujub M. Journal of Biological Chemistry, Vol. 293, Issue 23 https://doi.org/10.1074/jbc.RA118.001938	journal	April 2018
Titin Determines the Frank-Starling Relation in Early Diastole Helmes, Michiel; Lim, Chee Chew; Liao, Ronglih The Journal of General Physiology, Vol. 121, Issue 2 https://doi.org/10.1085/jgp.20028652	journal	January 2003
Identification of an N2 line protein of striated muscle. Wang, K.; Williamson, C. L. Proceedings of the National Academy of Sciences, Vol. 77, Issue 6 https://doi.org/10.1073/pnas.77.6.3254	journal	June 1980
Visualization of cardiac muscle thin filaments and measurement of their lengths by electron tomography Burgoyne, Thomas; Muhamad, Farina; Luther, Pradeep K. Cardiovascular Research, Vol. 77, Issue 4 https://doi.org/10.1093/cvr/cvm117	journal	January 2008
Titin Isoform Variance and Length Dependence of Activation in Skinned Bovine Cardiac Muscle Fukuda, Norio; Wu, Yiming; Farman, Gerrie The Journal of Physiology, Vol. 553, Issue 1 https://doi.org/10.1113/jphysiol.2003.049759	journal	November 2003
Steric-model for activation of muscle thin filaments 1 1 Edited by P.E. Wright Vibert, Peter; Craig, Roger; Lehman, William Journal of Molecular Biology, Vol. 266, Issue 1 https://doi.org/10.1006/jmbi.1996.0800	journal	February 1997
A comparison of muscle thin filament models obtained from electron microscopy reconstructions and low-angle X-ray fibre diagrams from non-overlap muscle Poole, Katrina J. V.; Lorenz, Michael; Evans, Gwyndaf Journal of Structural Biology, Vol. 155, Issue 2 https://doi.org/10.1016/j.jsb.2006.02.020	journal	August 2006
Resolution and uniqueness of estimated parameters of a model of thin filament regulation in solution Mijailovich, Srboljub M.; Li, Xiaochuan; del Álamo, Juan C. Computational Biology and Chemistry, Vol. 34, Issue 1 https://doi.org/10.1016/j.compbiolchem.2009.11.002	journal	February 2010
Cooperativity and Switching within the Three-State Model of Muscle Regulation ^† Maytum, Robin; Lehrer, Sherwin S.; Geeves, Michael A. Biochemistry, Vol. 38, Issue 3 https://doi.org/10.1021/bi981603e	journal	January 1999
Nebulin Alters Cross-bridge Cycling Kinetics and Increases Thin Filament Activation: A NOVEL MECHANISM FOR INCREASING TENSION AND REDUCING TENSION COST Chandra, Murali; Mamidi, Ranganath; Ford, Steven Journal of Biological Chemistry, Vol. 284, Issue 45 https://doi.org/10.1074/jbc.M109.049718	journal	September 2009
Thick Filament Mechano-Sensing in Skeletal and Cardiac Muscles: A Common Mechanism Able to Adapt the Energetic Cost of the Contraction to the Task Piazzesi, Gabriella; Caremani, Marco; Linari, Marco Frontiers in Physiology, Vol. 9 https://doi.org/10.3389/fphys.2018.00736	journal	June 2018
Nebulin deficiency in adult muscle causes sarcomere defects and muscle-type-dependent changes in trophicity: novel insights in nemaline myopathy Li, Frank; Buck, Danielle; De Winter, Josine Human Molecular Genetics, Vol. 24, Issue 18 https://doi.org/10.1093/hmg/ddv243	journal	June 2015
Three-dimensional stochastic model of actin–myosin binding in the sarcomere lattice Mijailovich, Srboljub M.; Kayser-Herold, Oliver; Stojanovic, Boban The Journal of General Physiology, Vol. 148, Issue 6 https://doi.org/10.1085/jgp.201611608	journal	November 2016
The Giant Muscle Protein Titin is an Adjustable Molecular Spring Granzier, Henk L.; Labeit, Siegfried Exercise and Sport Sciences Reviews, Vol. 34, Issue 2 https://doi.org/10.1249/00003677-200604000-00002	journal	January 2006
Mechanically Driven Contour-Length Adjustment in Rat Cardiac Titin’s Unique N2B Sequence: Titin Is an Adjustable Spring Helmes, M.; Trombitás, K.; Centner, T. Circulation Research, Vol. 84, Issue 11 https://doi.org/10.1161/01.res.84.11.1339	journal	June 1999
The Shape and Flexibility of Tropomyosin Coiled Coils: Implications for Actin Filament Assembly and Regulation Li, Xiaochuan (Edward); Holmes, Kenneth C.; Lehman, William Journal of Molecular Biology, Vol. 395, Issue 2 https://doi.org/10.1016/j.jmb.2009.10.060	journal	January 2010
Roles of Titin in the Structure and Elasticity of the Sarcomere Tskhovrebova, Larissa; Trinick, John Journal of Biomedicine and Biotechnology, Vol. 2010 https://doi.org/10.1155/2010/612482	journal	January 2010
Nebulin, a major player in muscle health and disease Labeit, Siegfried; Ottenheijm, Coen A. C.; Granzier, Henk The FASEB Journal, Vol. 25, Issue 3 https://doi.org/10.1096/fj.10-157412	journal	March 2011
Sizes of components in frog skeletal muscle measured by methods of stereology Mobley, B. A. The Journal of General Physiology, Vol. 66, Issue 1 https://doi.org/10.1085/jgp.66.1.31	journal	July 1975
The myofilament elasticity and its effect on kinetics of force generation by the myosin motor Piazzesi, Gabriella; Dolfi, Mario; Brunello, Elisabetta Archives of Biochemistry and Biophysics, Vol. 552-553 https://doi.org/10.1016/j.abb.2014.02.017	journal	June 2014
Cooperative Regulation of Myosin-Actin Interactions by a Continuous Flexible Chain II: Actin-Tropomyosin-Troponin and Regulation by Calcium Smith, D. A.; Geeves, M. A. Biophysical Journal, Vol. 84, Issue 5 https://doi.org/10.1016/S0006-3495(03)70041-1	journal	May 2003
Myofilament length dependent activation de Tombe, Pieter P.; Mateja, Ryan D.; Tachampa, Kittipong Journal of Molecular and Cellular Cardiology, Vol. 48, Issue 5 https://doi.org/10.1016/j.yjmcc.2009.12.017	journal	May 2010
Titin-based tension in the cardiac sarcomere: Molecular origin and physiological adaptations Anderson, Brian R.; Granzier, Henk L. Progress in Biophysics and Molecular Biology, Vol. 110, Issue 2-3 https://doi.org/10.1016/j.pbiomolbio.2012.08.003	journal	October 2012
The role of super-relaxed myosin in skeletal and cardiac muscle McNamara, James W.; Li, Amy; dos Remedios, Cristobal G. Biophysical Reviews, Vol. 7, Issue 1 https://doi.org/10.1007/s12551-014-0151-5	journal	December 2014
The amino acid sequence of bovine cardiac troponin-C. Comparison with rabbit skeletal troponin-C van Eerd, Jean-Paul; Takahashi, Kenji Biochemical and Biophysical Research Communications, Vol. 64, Issue 1 https://doi.org/10.1016/0006-291X(75)90227-2	journal	May 1975
Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy Hinson, J. T.; Chopra, A.; Nafissi, N. Science, Vol. 349, Issue 6251 https://doi.org/10.1126/science.aaa5458	journal	August 2015
Nebulin increases thin filament stiffness and force per cross-bridge in slow-twitch soleus muscle fibers Kawai, Masataka; Karam, Tarek S.; Kolb, Justin The Journal of General Physiology, Vol. 150, Issue 11 https://doi.org/10.1085/jgp.201812104	journal	October 2018
Nebulin stiffens the thin filament and augments cross-bridge interaction in skeletal muscle Kiss, Balázs; Lee, Eun-Jeong; Ma, Weikang Proceedings of the National Academy of Sciences, Vol. 115, Issue 41 https://doi.org/10.1073/pnas.1804726115	journal	September 2018
Genetic Variation in Titin in Arrhythmogenic Right Ventricular Cardiomyopathy–Overlap Syndromes Taylor, Matthew; Graw, Sharon; Sinagra, Gianfranco Circulation, Vol. 124, Issue 8 https://doi.org/10.1161/CIRCULATIONAHA.110.005405	journal	August 2011
Tropomyosin Length and Two-stranded F-actin Flexibility in the Thin Filament Censullo, Richard; Cheung, Herbert C. Journal of Molecular Biology, Vol. 243, Issue 3 https://doi.org/10.1006/jmbi.1994.1677	journal	October 1994
Persistence Length of Human Cardiac α-Tropomyosin Measured by Single Molecule Direct Probe Microscopy Loong, Campion K. P.; Zhou, Huan-Xiang; Chase, P. Bryant PLoS ONE, Vol. 7, Issue 6 https://doi.org/10.1371/journal.pone.0039676	journal	June 2012
Myosin filament activation in the heart is tuned to the mechanical task Reconditi, Massimo; Caremani, Marco; Pinzauti, Francesca Proceedings of the National Academy of Sciences, Vol. 114, Issue 12 https://doi.org/10.1073/pnas.1619484114	journal	March 2017
Nebulin regulates thin filament length, contractility, and Z-disk structure in vivo Witt, Christian C.; Burkart, Christoph; Labeit, Dietmar The EMBO Journal, Vol. 25, Issue 16 https://doi.org/10.1038/sj.emboj.7601242	journal	August 2006
Evidence for cross-bridge attachment in relaxed muscle at low ionic strength. Brenner, B.; Schoenberg, M.; Chalovich, J. M. Proceedings of the National Academy of Sciences, Vol. 79, Issue 23 https://doi.org/10.1073/pnas.79.23.7288	journal	December 1982
Compliant Realignment of Binding Sites in Muscle: Transient Behavior and Mechanical Tuning Daniel, Thomas L.; Trimble, Alan C.; Bryant Chase, P. Biophysical Journal, Vol. 74, Issue 4 https://doi.org/10.1016/s0006-3495(98)77875-0	journal	April 1998
Cooperative [Ca2+]-Dependent Regulation of the Rate of Myosin Binding to Actin: Solution Data and the Tropomyosin Chain Model Geeves, Michael; Griffiths, Hugh; Mijailovich, Srboljub Biophysical Journal, Vol. 100, Issue 11 https://doi.org/10.1016/j.bpj.2011.04.020	journal	June 2011
Filament Compliance Influences Cooperative Activation of Thin Filaments and the Dynamics of Force Production in Skeletal Muscle Tanner, Bertrand C. W.; Daniel, Thomas L.; Regnier, Michael PLoS Computational Biology, Vol. 8, Issue 5 https://doi.org/10.1371/journal.pcbi.1002506	journal	May 2012
Nebulette: A 107 kD nebulin-like protein in cardiac muscle Moncman, Carole L.; Wang, Kuan Cell Motility and the Cytoskeleton, Vol. 32, Issue 3 https://doi.org/10.1002/cm.970320305	journal	January 1995
Titin and the sarcomere symmetry paradox11Edited by J. Karn Liversage, A. D.; Holmes, D.; Knight, P. J. Journal of Molecular Biology, Vol. 305, Issue 3 https://doi.org/10.1006/jmbi.2000.4279	journal	January 2001
Proposed Mechanism of Force Generation in Striated Muscle Huxley, A. F.; Simmons, R. M. Nature, Vol. 233, Issue 5321 https://doi.org/10.1038/233533a0	journal	October 1971
Titin Extensibility In Situ: Entropic Elasticity of Permanently Folded and Permanently Unfolded Molecular Segments Trombitás, Karoly; Greaser, Marion; Labeit, Siegfried The Journal of Cell Biology, Vol. 140, Issue 4 https://doi.org/10.1083/jcb.140.4.853	journal	February 1998
Experimentally Increasing Titin Compliance in a Novel Mouse Model Attenuates the Frank-Starling Mechanism But Has a Beneficial Effect on Diastole Methawasin, Mei; Hutchinson, Kirk R.; Lee, Eun-Jeong Circulation, Vol. 129, Issue 19 https://doi.org/10.1161/CIRCULATIONAHA.113.005610	journal	May 2014
Experimentally Increasing the Compliance of Titin Through RNA Binding Motif-20 (RBM20) Inhibition Improves Diastolic Function In a Mouse Model of Heart Failure With Preserved Ejection Fraction Methawasin, Mei; Strom, Joshua G.; Slater, Rebecca E. Circulation, Vol. 134, Issue 15 https://doi.org/10.1161/CIRCULATIONAHA.116.023003	journal	October 2016
Myosin binding-induced cooperative activation of the thin filament in cardiac myocytes and skeletal muscle fibers Metzger, J. M. Biophysical Journal, Vol. 68, Issue 4 https://doi.org/10.1016/S0006-3495(95)80316-4	journal	April 1995
Understanding the Organisation and Role of Myosin Binding Protein C in Normal Striated Muscle by Comparison with MyBP-C Knockout Cardiac Muscle Luther, Pradeep K.; Bennett, Pauline M.; Knupp, Carlo Journal of Molecular Biology, Vol. 384, Issue 1 https://doi.org/10.1016/j.jmb.2008.09.013	journal	December 2008
X-ray diffraction from nonuniformly stretched helical molecules Prodanovic, Momcilo; Irving, Thomas C.; Mijailovich, Srboljub M. Journal of Applied Crystallography, Vol. 49, Issue 3 https://doi.org/10.1107/S1600576716003757	journal	April 2016
Structure of co-crystals of tropomyosin and troponin White, Steven P.; Cohen, Carolyn; Phillips Jr, George N. Nature, Vol. 325, Issue 6107 https://doi.org/10.1038/325826a0	journal	February 1987
Nebulin plays a direct role in promoting strong actin-myosin interactions Bang, Marie-Louise; Caremani, Marco; Brunello, Elisabetta The FASEB Journal, Vol. 23, Issue 12 https://doi.org/10.1096/fj.09-137729	journal	December 2009
Mechanical properties of tropomyosin and implications for muscle regulation Phillips, George N.; Chacko, Susan Biopolymers, Vol. 38, Issue 1 https://doi.org/10.1002/(sici)1097-0282(199601)38:1<89::aid-bip7>3.0.co;2-s	journal	January 1996
A Spatially Explicit Model Shows How Titin Stiffness Modulates Muscle Mechanics and Energetics Powers, Joseph D.; Williams, C. David; Regnier, Michael Integrative and Comparative Biology, Vol. 58, Issue 2 https://doi.org/10.1093/icb/icy055	journal	June 2018
Truncation of Titin’s Elastic PEVK Region Leads to Cardiomyopathy With Diastolic Dysfunction Granzier, Henk L.; Radke, Michael H.; Peng, Jun Circulation Research, Vol. 105, Issue 6 https://doi.org/10.1161/CIRCRESAHA.109.200964	journal	September 2009
The length–tension curve in muscle depends on lattice spacing Williams, C. David; Salcedo, Mary K.; Irving, Thomas C. Proceedings of the Royal Society B: Biological Sciences, Vol. 280, Issue 1766 https://doi.org/10.1098/rspb.2013.0697	journal	September 2013
Refinement of the F-Actin Model against X-ray Fiber Diffraction Data by the Use of a Directed Mutation Algorithm Lorenz, Michael; Popp, David; Holmes, Kenneth C. Journal of Molecular Biology, Vol. 234, Issue 3 https://doi.org/10.1006/jmbi.1993.1628	journal	December 1993
Path-integral theory of an axially confined worm-like chain Smith, D. A. Journal of Physics A: Mathematical and General, Vol. 34, Issue 21 https://doi.org/10.1088/0305-4470/34/21/307	journal	May 2001
Variation of thin filament length in heart muscle Robinson, Thomas F.; Winegrad, Saul Nature, Vol. 267, Issue 5606 https://doi.org/10.1038/267074a0	journal	May 1977
Cooperative regulation of myosin-S1 binding to actin filaments by a continuous flexible Tm–Tn chain Mijailovich, Srboljub M.; Kayser-Herold, Oliver; Li, Xiaochuan European Biophysics Journal, Vol. 41, Issue 12 https://doi.org/10.1007/s00249-012-0859-8	journal	October 2012
Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy Ceyhan-Birsoy, O.; Agrawal, P. B.; Hidalgo, C. Neurology, Vol. 81, Issue 14 https://doi.org/10.1212/WNL.0b013e3182a6ca62	journal	August 2013
Fast Skeletal Muscle Troponin Activation Increases Force of Mouse Fast Skeletal Muscle and Ameliorates Weakness Due to Nebulin-Deficiency Lee, Eun-Jeong; De Winter, Josine M.; Buck, Danielle PLoS ONE, Vol. 8, Issue 2 https://doi.org/10.1371/journal.pone.0055861	journal	February 2013
A Simple Model with Myofilament Compliance Predicts Activation-Dependent Crossbridge Kinetics in Skinned Skeletal Fibers Martyn, D. A.; Chase, P. B.; Regnier, M. Biophysical Journal, Vol. 83, Issue 6 https://doi.org/10.1016/s0006-3495(02)75342-3	journal	December 2002
Elasticity of $α$ -Helical Coiled Coils Wolgemuth, Charles W.; Sun, Sean X. Physical Review Letters, Vol. 97, Issue 24 https://doi.org/10.1103/PhysRevLett.97.248101	journal	December 2006
Mouse intact cardiac myocyte mechanics: cross-bridge and titin-based stress in unactivated cells King, Nicholas M. P.; Methawasin, Methajit; Nedrud, Joshua The Journal of General Physiology, Vol. 137, Issue 1 https://doi.org/10.1085/jgp.201010499	journal	December 2010
Length-dependent activation: its effect on the length-tension relation in cat ventricular muscle. Lakatta, E. G.; Jewell, B. R. Circulation Research, Vol. 40, Issue 3 https://doi.org/10.1161/01.RES.40.3.251	journal	March 1977
Electron Microscopy and Persistence Length Analysis of Semi-Rigid Smooth Muscle Tropomyosin Strands Sousa, Duncan; Cammarato, Anthony; Jang, Ken Biophysical Journal, Vol. 99, Issue 3 https://doi.org/10.1016/j.bpj.2010.05.004	journal	August 2010
Extensibility and Symmetry of Actin Filaments in Contracting Muscles Bordas, J.; Svensson, A.; Rothery, M. Biophysical Journal, Vol. 77, Issue 6 https://doi.org/10.1016/S0006-3495(99)77150-X	journal	December 1999
The Filament Lattice of Striated Muscle Millman, Barry M. Physiological Reviews, Vol. 78, Issue 2 https://doi.org/10.1152/physrev.1998.78.2.359	journal	April 1998
Calcium binding to cardiac troponin C Leavis, P. C.; Kraft, Ellen L. Archives of Biochemistry and Biophysics, Vol. 186, Issue 2 https://doi.org/10.1016/0003-9861(78)90453-8	journal	March 1978
Genotype?phenotype correlations in nemaline myopathy caused by mutations in the genes for nebulin and skeletal muscle ?-actin Wallgrenpettersson, C. Neuromuscular Disorders, Vol. 14, Issue 8-9 https://doi.org/10.1016/j.nmd.2004.03.006	journal	September 2004
Modeling the Actin.myosin ATPase Cross-Bridge Cycle for Skeletal and Cardiac Muscle Myosin Isoforms Mijailovich, Srbolujub M.; Nedic, Djordje; Svicevic, Marina Biophysical Journal, Vol. 112, Issue 5 https://doi.org/10.1016/j.bpj.2017.01.021	journal	March 2017
Altered myofilament function depresses force generation in patients with nebulin-based nemaline myopathy (NEM2) Ottenheijm, Coen A. C.; Hooijman, Pleuni; DeChene, Elizabeth T. Journal of Structural Biology, Vol. 170, Issue 2 https://doi.org/10.1016/j.jsb.2009.11.013	journal	May 2010
Cooperative Regulation of Myosin-Actin Interactions by a Continuous Flexible Chain I: Actin-Tropomyosin Systems Smith, D. A.; Maytum, R.; Geeves, M. A. Biophysical Journal, Vol. 84, Issue 5 https://doi.org/10.1016/S0006-3495(03)70040-X	journal	May 2003
Sarcomere-length dependence of lattice volume and radial mass transfer of myosin cross-bridges in rat papillary muscle Yagi, Naoto; Okuyama, Hiroshi; Toyota, Hiroko Pfl�gers Archiv European Journal of Physiology, Vol. 448, Issue 2 https://doi.org/10.1007/s00424-004-1243-z	journal	May 2004
Distinct contributions of the thin and thick filaments to length-dependent activation in heart muscle Zhang, Xuemeng; Kampourakis, Thomas; Yan, Ziqian eLife, Vol. 6 https://doi.org/10.7554/elife.24081	journal	February 2017
Single Molecule Force Spectroscopy on Titin Implicates Immunoglobulin Domain Stability as a Cardiac Disease Mechanism Anderson, Brian R.; Bogomolovas, Julius; Labeit, Siegfried Journal of Biological Chemistry, Vol. 288, Issue 8 https://doi.org/10.1074/jbc.M112.401372	journal	January 2013
Mutations of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy Gerull, Brenda; Gramlich, Michael; Atherton, John Nature Genetics, Vol. 30, Issue 2 https://doi.org/10.1038/ng815	journal	January 2002
Cardiac Titin and Heart Disease LeWinter, Martin M.; Granzier, Henk L. Journal of Cardiovascular Pharmacology, Vol. 63, Issue 3 https://doi.org/10.1097/FJC.0000000000000007	journal	January 2014
Thin filament length dysregulation contributes to muscle weakness in nemaline myopathy patients with nebulin deficiency Ottenheijm, C. A. C.; Witt, C. C.; Stienen, G. J. Human Molecular Genetics, Vol. 18, Issue 13 https://doi.org/10.1093/hmg/ddp168	journal	April 2009
Myofilament lattice spacing as a function of sarcomere length in isolated rat myocardium Irving, Thomas C.; Konhilas, John; Perry, Darold American Journal of Physiology-Heart and Circulatory Physiology, Vol. 279, Issue 5 https://doi.org/10.1152/ajpheart.2000.279.5.H2568	journal	November 2000
The relationship between curvature, flexibility and persistence length in the tropomyosin coiled-coil Li, Xiaochuan (Edward); Lehman, William; Fischer, Stefan Journal of Structural Biology, Vol. 170, Issue 2 https://doi.org/10.1016/j.jsb.2010.01.016	journal	May 2010
Myosin Head Configurations in Resting and Contracting Murine Skeletal Muscle Ma, Weikang; Gong, Henry; Irving, Thomas International Journal of Molecular Sciences, Vol. 19, Issue 9 https://doi.org/10.3390/ijms19092643	journal	September 2018
Congenital Titinopathy: Comprehensive characterization and pathogenic insights Oates, Emily C.; Jones, Kristi J.; Donkervoort, Sandra Annals of Neurology, Vol. 83, Issue 6 https://doi.org/10.1002/ana.25241	journal	May 2018
Passive tension in cardiac muscle: contribution of collagen, titin, microtubules, and intermediate filaments Granzier, H. L.; Irving, T. C. Biophysical Journal, Vol. 68, Issue 3 https://doi.org/10.1016/s0006-3495(95)80278-x	journal	March 1995
Nebulin as a length regulator of thin filaments of vertebrate skeletal muscles: correlation of thin filament length, nebulin size, and epitope profile Kruger, M. The Journal of Cell Biology, Vol. 115, Issue 1 https://doi.org/10.1083/jcb.115.1.97	journal	October 1991
SH3 in muscles: solution structure of the SH3 domain from nebulin Politou, Anastasia S.; Millevoi, Stefania; Gautel, Mathias Journal of Molecular Biology, Vol. 276, Issue 1 https://doi.org/10.1006/jmbi.1997.1521	journal	February 1998
Role of titin in cardiomyopathy: from DNA variants to patient stratification Ware, James S.; Cook, Stuart A. Nature Reviews Cardiology, Vol. 15, Issue 4 https://doi.org/10.1038/nrcardio.2017.190	journal	December 2017
Interactions Between Connected Half-Sarcomeres Produce Emergent Mechanical Behavior in a Mathematical Model of Muscle Campbell, Kenneth S. Biophysical Journal, Vol. 98, Issue 3 https://doi.org/10.1016/j.bpj.2009.12.792	journal	January 2010
Evidence that nebulin is a protein-ruler in muscle thin filaments Labeit, S.; Gibson, T.; Lakey, A. FEBS Letters, Vol. 282, Issue 2 https://doi.org/10.1016/0014-5793(91)80503-U	journal	May 1991
X-ray diffraction measurements of the extensibility of actin and myosin filaments in contracting muscle Huxley, H. E.; Stewart, A.; Sosa, H. Biophysical Journal, Vol. 67, Issue 6 https://doi.org/10.1016/S0006-3495(94)80728-3	journal	December 1994
Architecture and function in the muscle sarcomere Squire, John M. Current Opinion in Structural Biology, Vol. 7, Issue 2 https://doi.org/10.1016/S0959-440X(97)80033-4	journal	April 1997
Novel mutations in NEB cause abnormal nebulin expression and markedly impaired muscle force generation in severe nemaline myopathy Lawlor, Michael W.; Ottenheijm, Coen A.; Lehtokari, Vilma-Lotta Skeletal Muscle, Vol. 1, Issue 1 https://doi.org/10.1186/2044-5040-1-23	journal	January 2011
Comparison between the sarcomere length-force relations of intact and skinned trabeculae from rat right ventricle. Influence of calcium concentrations on these relations. Kentish, J. C.; ter Keurs, H. E.; Ricciardi, L. Circulation Research, Vol. 58, Issue 6 https://doi.org/10.1161/01.RES.58.6.755	journal	June 1986
Titin strain contributes to the Frank–Starling law of the heart by structural rearrangements of both thin- and thick-filament proteins Ait-Mou, Younss; Hsu, Karen; Farman, Gerrie P. Proceedings of the National Academy of Sciences, Vol. 113, Issue 8 https://doi.org/10.1073/pnas.1516732113	journal	February 2016
Titin: major myofibrillar components of striated muscle. Wang, K.; McClure, J.; Tu, A. Proceedings of the National Academy of Sciences, Vol. 76, Issue 8 https://doi.org/10.1073/pnas.76.8.3698	journal	August 1979
Regulation of the interaction between actin and myosin subfragment 1: evidence for three states of the thin filament McKillop, D. F.; Geeves, M. A. Biophysical Journal, Vol. 65, Issue 2 https://doi.org/10.1016/S0006-3495(93)81110-X	journal	August 1993
The Stiffness of Skeletal Muscle in Isometric Contraction and Rigor: The Fraction of Myosin Heads Bound to Actin Linari, Marco; Dobbie, Ian; Reconditi, Massimo Biophysical Journal, Vol. 74, Issue 5 https://doi.org/10.1016/S0006-3495(98)77954-8	journal	May 1998
The Complete Mouse Nebulin Gene Sequence and the Identification of Cardiac Nebulin Kazmierski, Steven T.; Antin, Parker B.; Witt, Christian C. Journal of Molecular Biology, Vol. 328, Issue 4 https://doi.org/10.1016/S0022-2836(03)00348-6	journal	May 2003
Direct measurement of stiffness of single actin filaments with and without tropomyosin by in vitro nanomanipulation. Kojima, H.; Ishijima, A.; Yanagida, T. Proceedings of the National Academy of Sciences, Vol. 91, Issue 26 https://doi.org/10.1073/pnas.91.26.12962	journal	December 1994
Titin-based modulation of active tension and interfilament lattice spacing in skinned rat cardiac muscle Fukuda, Norio; Wu, Yiming; Farman, Gerrie Pfl�gers Archiv - European Journal of Physiology, Vol. 449, Issue 5 https://doi.org/10.1007/s00424-004-1354-6	journal	November 2004
Sarcoplasmic reticulum calcium uptake and speed of relaxation are depressed in nebulin-free skeletal muscle Ottenheijm, Coen A. C.; Fong, Chi; Vangheluwe, Peter The FASEB Journal, Vol. 22, Issue 8 https://doi.org/10.1096/fj.07-104372	journal	August 2008
Exploration of pathomechanisms triggered by a single-nucleotide polymorphism in titin's I-band: the cardiomyopathy-linked mutation T2580I Bogomolovas, Julius; Fleming, Jennifer R.; Anderson, Brian R. Open Biology, Vol. 6, Issue 9 https://doi.org/10.1098/rsob.160114	journal	September 2016
The Hill Model for Binding Myosin S1 to Regulated Actin Is not Equivalent to the McKillop–Geeves Model Mijailovich, Srboljub M.; Li, Xiaochuan; Griffiths, R. Hugh Journal of Molecular Biology, Vol. 417, Issue 1-2 https://doi.org/10.1016/j.jmb.2012.01.011	journal	March 2012
Molecular model of muscle contraction Duke, T. A. J. Proceedings of the National Academy of Sciences, Vol. 96, Issue 6 https://doi.org/10.1073/pnas.96.6.2770	journal	March 1999
Effects of cross-bridge compliance on the force-velocity relationship and muscle power output Fenwick, Axel J.; Wood, Alexander M.; Tanner, Bertrand C. W. PLOS ONE, Vol. 12, Issue 12 https://doi.org/10.1371/journal.pone.0190335	journal	December 2017
Interactions between Connected Half-Sarcomeres Produce Emergent Mechanical Behavior in a Mathematical Model of Muscle Campbell, Kenneth S. PLoS Computational Biology, Vol. 5, Issue 11 https://doi.org/10.1371/journal.pcbi.1000560	journal	November 2009
The measurement and dynamic implications of thin filament lengths in heart muscle. Robinson, T. F.; Winegrad, S. The Journal of Physiology, Vol. 286, Issue 1 https://doi.org/10.1113/jphysiol.1979.sp012640	journal	January 1979
Regulation of Contraction by the Thick Filaments in Skeletal Muscle Irving, Malcolm Biophysical Journal, Vol. 113, Issue 12 https://doi.org/10.1016/j.bpj.2017.09.037	journal	December 2017
Titin-Based Modulation of Calcium Sensitivity of Active Tension in Mouse Skinned Cardiac Myocytes Cazorla, Olivier; Wu, Yiming; Irving, Thomas C. Circulation Research, Vol. 88, Issue 10 https://doi.org/10.1161/hh1001.090876	journal	May 2001
Compliance of thin filaments in skinned fibers of rabbit skeletal muscle Higuchi, H.; Yanagida, T.; Goldman, Y. E. Biophysical Journal, Vol. 69, Issue 3 https://doi.org/10.1016/S0006-3495(95)79975-1	journal	September 1995
Titin Is a Major Human Disease Gene LeWinter, Martin M.; Granzier, Henk L. Circulation, Vol. 127, Issue 8 https://doi.org/10.1161/CIRCULATIONAHA.112.139717	journal	February 2013
Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy Pelin, K.; Hilpela, P.; Donner, K. Proceedings of the National Academy of Sciences, Vol. 96, Issue 5 https://doi.org/10.1073/pnas.96.5.2305	journal	March 1999
Connectin, an Elastic Protein of Muscle. Identification of “Titin” with Connectin1 Maruyama, Koscak; Kimura, Sumiko; Ohashi, Kazuyo The Journal of Biochemistry, Vol. 89, Issue 3 https://doi.org/10.1093/oxfordjournals.jbchem.a133249	journal	January 1981
Regulation of Contraction in Striated Muscle Gordon, A. M.; Homsher, E.; Regnier, M. Physiological Reviews, Vol. 80, Issue 2 https://doi.org/10.1152/physrev.2000.80.2.853	journal	January 2000
X-ray diffraction evidence for the extensibility of actin and myosin filaments during muscle contraction Wakabayashi, K.; Sugimoto, Y.; Tanaka, H. Biophysical Journal, Vol. 67, Issue 6 https://doi.org/10.1016/S0006-3495(94)80729-5	journal	December 1994
Single Particle Analysis of Relaxed and Activated Muscle Thin Filaments Pirani, Alnoor; Xu, Chen; Hatch, Victoria Journal of Molecular Biology, Vol. 346, Issue 3 https://doi.org/10.1016/j.jmb.2004.12.013	journal	February 2005
Molecular Mechanics of Cardiac Titin's PEVK and N2B Spring Elements Watanabe, Kaori; Nair, Preetha; Labeit, Dietmar Journal of Biological Chemistry, Vol. 277, Issue 13 https://doi.org/10.1074/jbc.m200356200	journal	March 2002
Length, force, and Ca(2+)-troponin C affinity in cardiac and slow skeletal muscle Wang, Y. P.; Fuchs, F. American Journal of Physiology-Cell Physiology, Vol. 266, Issue 4 https://doi.org/10.1152/ajpcell.1994.266.4.C1077	journal	April 1994
Force generation by skeletal muscle is controlled by mechanosensing in myosin filaments Linari, Marco; Brunello, Elisabetta; Reconditi, Massimo Nature, Vol. 528, Issue 7581 https://doi.org/10.1038/nature15727	journal	November 2015
Differential Expression of Cardiac Titin Isoforms and Modulation of Cellular Stiffness Cazorla, O.; Freiburg, A.; Helmes, M. Circulation Research, Vol. 86, Issue 1 https://doi.org/10.1161/01.RES.86.1.59	journal	January 2000
Truncations of Titin Causing Dilated Cardiomyopathy Herman, Daniel S.; Lam, Lien; Taylor, Matthew R. G. New England Journal of Medicine, Vol. 366, Issue 7 https://doi.org/10.1056/NEJMoa1110186	journal	February 2012
The calcium and magnesium binding sites on cardiac troponin and their role in the regulation of myofibrillar adenosine triphosphatase. Holroyde, M. J.; Robertson, S. P.; Johnson, J. D. Journal of Biological Chemistry, Vol. 255, Issue 24 https://doi.org/10.1016/S0021-9258(19)70187-2	journal	December 1980
Proteolytic fragments of troponin C. Localization of high and low affinity Ca2+ binding sites and interactions with troponin I and troponin T Leavis, P. C.; Rosenfeld, S. S.; Gergely, J. Journal of Biological Chemistry, Vol. 253, Issue 15 https://doi.org/10.1016/S0021-9258(17)30394-0	journal	August 1978
The calcium and magnesium binding sites on troponin and their role in the regulation of myofibrillar adenosine triphosphatase. Potter, J. D.; Gergely, J. Journal of Biological Chemistry, Vol. 250, Issue 12 https://doi.org/10.1016/S0021-9258(19)41347-1	journal	June 1975

Cited By (7)

Expressing a Z-disk nebulin fragment in nebulin-deficient mouse muscle: effects on muscle structure and function Li, Frank; Kolb, Justin; Crudele, Julie Skeletal Muscle, Vol. 10, Issue 1 https://doi.org/10.1186/s13395-019-0219-9	journal	January 2020
Progress on the regulation of myofibrillar function: Part 2 Granzier, Henk L.; Moss, Richard L. Journal of General Physiology, Vol. 151, Issue 5 https://doi.org/10.1085/jgp.201912380	journal	April 2019
Calcium-dependent titin–thin filament interactions in muscle: observations and theory Nishikawa, Kiisa; Dutta, Samrat; DuVall, Michael Journal of Muscle Research and Cell Motility, Vol. 41, Issue 1 https://doi.org/10.1007/s10974-019-09540-y	journal	July 2019
The mechanism of thin filament regulation: Models in conflict? Geeves, Michael A.; Lehrer, Sherwin S.; Lehman, William Journal of General Physiology, Vol. 151, Issue 11 https://doi.org/10.1085/jgp.201912446	journal	September 2019
Estimation of Forces on Actin Filaments in Living Muscle from X-ray Diffraction Patterns and Mechanical Data Mijailovich, Srboljub M.; Prodanovic, Momcilo; Irving, Thomas C. International Journal of Molecular Sciences, Vol. 20, Issue 23 https://doi.org/10.3390/ijms20236044	journal	November 2019
Elastic domains of giant proteins in striated muscle: Modeling compliance with rulers Chase, P. Bryant Journal of General Physiology, Vol. 151, Issue 5 https://doi.org/10.1085/jgp.201912345	journal	April 2019
Nebulin: big protein with big responsibilities Yuen, Michaela; Ottenheijm, Coen A. C. Journal of Muscle Research and Cell Motility, Vol. 41, Issue 1 https://doi.org/10.1007/s10974-019-09565-3	journal	January 2020

Similar Records

Comparative decline of the protein profiles of nebulin in response to denervation in skeletal muscle

Journal Article · Fri Oct 09 00:00:00 EDT 2015 · Biochemical and Biophysical Research Communications · OSTI ID:1558308

Wei, Jih-Hua; Chang, Nen-Chung; Chen, Sy-Ping; +3 more

Titin strain contributes to the Frank–Starling law of the heart by structural rearrangements of both thin- and thick-filament proteins

Journal Article · Mon Feb 08 00:00:00 EST 2016 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1558308

Ait-Mou, Younss; Hsu, Karen; Farman, Gerrie P.; +4 more

Nebulin stiffens the thin filament and augments cross-bridge interaction in skeletal muscle

Journal Article · Mon Sep 24 00:00:00 EDT 2018 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1558308

Kiss, Balázs; Lee, Eun-Jeong; Ma, Weikang; +5 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Contraction and Cell Motility
Myofilament Function

Title: Nebulin and titin modulate cross-bridge cycling and length-dependent calcium sensitivity

Citation Formats

References (130)

Cited By (7)

Similar Records

Related Subjects