Review
Physiology
J. M. Chalovich, L. Zhu, D. Johnson
Summary: Striated muscle contraction is inhibited by several actin associated proteins, and the binding of Ca2+ can relieve this inhibition. Tropomyosin can be positioned in three different states on actin, which are associated with different functional states of the contractile system. Mutants of troponin can stabilize different states and provide tools for studying individual states. The C-terminal region of troponin T plays a unique role in limiting Ca2+ activation.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Katarzyna Robaszkiewicz, Julia Wrobel, Joanna Moraczewska
Summary: Defects in maintaining the length of actin filaments may contribute to skeletal muscle diseases associated with mutations in tropomyosin genes. The p.R91C variant in Tpm3.12, a tropomyosin isoform expressed in slow-twitch muscle fibers, impairs the regulation of actin severing and depolymerization by cofilin-2, leading to abnormal actin filament turnover. Additionally, troponin also inhibits actin severing and depolymerization to some extent.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Natalia A. Koubassova, Andrey K. Tsaturyan
Summary: Contraction of cardiac muscle is regulated by Ca2+ ions via regulatory proteins, troponin (Tn), and tropomyosin (Tpm) associated with the thin (actin) filaments in myocardial sarcomeres. Recent cryo-electron microscopy (cryo-EM) models of the complex allow one to study the dynamic and mechanical properties of the complex using molecular dynamics (MD). However, further refinement of the models is needed to improve the protein-protein interaction in some regions of the complex, as suggested by problems revealed from the MD simulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biophysics
Larry S. Tobacman
Summary: Recent advances in understanding the structural basis of troponin-tropomyosin's regulation of striated muscle contraction, particularly through cryo-electron microscopy data, have revealed compelling atomic models for both apo- and Ca2+-saturated states. Subsequent analyses have further elucidated these findings, showing the hindering effects of troponin and tropomyosin on myosin-actin binding in relaxed muscle and the specific bindings in the Ca2+-saturated state.
BIOPHYSICAL JOURNAL
(2021)
Article
Cell Biology
Shoichiro Ono, Mario Lewis, Kanako Ono
Summary: This study demonstrates the mutual dependence of tropomodulin and tropomyosin in sarcomere assembly and regulation of actin filaments in the nematode Caenorhabditis elegans.
EUROPEAN JOURNAL OF CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Cristina M. Risi, Ian Pepper, Betty Belknap, Maicon Landim-Vieira, Howard D. White, Kelly Dryden, Jose R. Pinto, P. Bryant Chase, Vitold E. Galkin
Summary: The study reveals the structural composition of cardiac thin filaments under systolic Ca2+ levels, showing that the two strands of the thin filament consist of troponin complexes with different binding states and short-range cooperativity. These findings suggest a mechanism by which cardiac muscle is regulated by narrow range Ca2+ fluctuations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Victoria V. Nefedova, Galina V. Kopylova, Daniil V. Shchepkin, Anastasia M. Kochurova, Olga I. Kechko, Vera A. Borzova, Natalia S. Ryabkova, Ivan A. Katrukha, Vladimir A. Mitkevich, Sergey Y. Bershitsky, Dmitrii I. Levitsky, Alexander M. Matyushenko
Summary: By investigating the role of cardiac troponin T (TnT) in Tpm mutations associated with cardiomyopathy, it was found that TnT1 stabilizes Tpm WT and all mutants except Tpm M8R. The study also demonstrated that Tpm mutations likely exert their pathogenic effects through interactions with Tn, cardiac myosin, or other protein partners.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Physiology
Zabed Mahmud, Svetlana Tikunova, Natalya Belevych, Cory S. Wagg, Pavel Zhabyeyev, Philip B. Liu, David V. Rasicci, Christopher M. Yengo, Gavin Y. Oudit, Gary D. Lopaschuk, Peter J. Reiser, Jonathan P. Davis, Peter M. Hwang
Summary: Researchers have developed a small molecule, RPI-194, that can enhance cardiac muscle contraction and potentially be used to treat systolic heart failure.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Elumalai Pavadai, Michael J. Rynkiewicz, Zeyu Yang, Ian R. Gould, Steven B. Marston, William Lehman
Summary: This study reveals the phosphorylation regulation mechanism of cardiac-specific tropomyosin by utilizing protein modeling and molecular dynamics simulation. The results suggest that phosphorylated residues may interact closely with tropomyosin and the N-lobe of TnC, thereby affecting cardiac muscle contraction and relaxation.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Hui-Fang Liang, Xiang-dong Li
Summary: This study reveals that besides Ca2+, other regulatory mechanisms are required for the full activation of locust flight muscle.
INSECT MOLECULAR BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Lorenzo Marcucci
Summary: Contraction in striated muscle is traditionally regulated by calcium-mediated structural changes in the thin filaments, but a new paradigm suggests that both the thin and thick filaments must be activated to generate force. There is growing evidence that thick filament activation plays a role in fine regulation of muscle and its impairment is associated with severe pathologies. This review focuses on the mechanosensing mechanism that activates inactive motors based on tension generated by active motors, highlighting the bi-directional feedback on muscle mechanics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Physiology
Michael J. Rynkiewicz, Elumalai Pavadai, William Lehman
Summary: This article investigates the mechanism of calcium-dependent regulation of striated muscle contraction and reveals key intermolecular interactions and conformational changes through modeling and molecular dynamics simulation. It is of great significance for understanding mutation-induced contractile dysfunction related to muscle diseases.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biology
Cameron Hill, Elisabetta Brunello, Luca Fusi, Jesus G. Ovejero, Malcolm Irving
Summary: The study revealed a sequence of structural changes during muscle activation, including thin filament activation, disruption of the helical array of myosin motors, release of myosin motor domains from the folded conformation, and actin attachment. Physiological force generation in skeletal muscle twitch response is limited by incomplete activation of the thick filament and rapid inactivation of both filaments.
Article
Chemistry, Physical
Allison B. Mason, Jil C. Tardiff, Steven D. Schwartz
Summary: The interaction between cardiac troponin C (cTnC) and cardiac troponin I (cTnI) plays an important regulatory role in the contraction of cardiomyocytes. This study used metadynamics to calculate the free-energy surface of two transitions in the cardiac thin filament (CTF), and found that calcium ion stabilizes the open conformation of cTnC and that cTnC opening stabilizes the C-terminus of cTnI during its dissociation from actin.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Multidisciplinary Sciences
Hamidreza Rahmani, Wen Ma, Zhongjun Hu, Nadia Daneshparvar, Dianne W. Taylor, J. Andrew McCammon, Thomas C. Irving, Robert J. Edwards, Kenneth A. Taylor
Summary: The atomic structure of myosin tail in thick filaments isolated from Lethocerus indicus flight muscle is asymmetric, with differences in skip regions and nonhelical C termini. The study provides insights into the uncoiling of coiled-coils at the head-tail junction and sheds light on the complex roles of thick filaments in muscle contraction across species.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biotechnology & Applied Microbiology
Olesya Plazyo, Weilong Hao, Jian-Ping Jin
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2020)
Article
Physiology
Han-Zhong Feng, J. -P. Jin
EXPERIMENTAL PHYSIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Felipe Hornos, Han-Zhong Feng, Bruno Rizzuti, Martina Palomino-Schatzlein, David Wieczorek, Jose L. Neira, J. -P. Jin
Summary: The conserved C-terminal end segment of troponin I (TnI) regulates muscle relaxation by reducing the Ca2+-sensitivity of myofibrils and promoting relaxation without decreasing force production. The isolated C-terminal 27 amino acid peptide from human cardiac TnI (HcTnI-C27) interacts with tropomyosin and can potentially improve diastolic function of the heart, making it a promising therapeutic approach.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Genetics & Heredity
Dongshan Yang, Xiubin Liang, Brooke Pallas, Mark Hoenerhoff, Zhuoying Ren, Renzhi Han, Jifeng Zhang, Y. Eugene Chen, Jian-Ping Jin, Fei Sun, Jie Xu
Summary: This study successfully generated CFTR-Delta F508 rabbits using CRISPR/Cas9 technology and confirmed their germline transmission. This provides a new tool for research on cystic fibrosis models and lays the foundation for future biomedical studies.
FRONTIERS IN GENETICS
(2021)
Article
Surgery
Tzu-Bou Hsieh, Han-Zhong Feng, Jian-Ping Jin
Summary: Deletion of calponin 2 effectively reduces postoperative peritoneal adhesion, presenting a novel molecular target for clinical prevention.
Calponin 2 KO mice developed significantly less postoperative peritoneal adhesions with reduced infiltration of F4/80(+) macrophages at the adhesion sites and less myofibroblast differentiation compared to WT mice.
JOURNAL OF INVESTIGATIVE SURGERY
(2022)
Article
Cell Biology
Masataka Kawai, Jian-Ping Jin
Summary: Vertebrate cardiac muscle exhibits larger systolic force with increasing end diastolic chamber volume, known as Frank-Starling Law or length dependent activation (LDA). This phenomenon is explained by factors such as lattice spacing, increased Ca2+ sensitivity, titin-mediated rearrangement of myosin heads, and stretch activation, which may share mechanisms with insect muscles. Sarcomere stiffness caused by titin in vertebrate muscles is a key contributor to LDA.
JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY
(2021)
Article
Health Care Sciences & Services
Xiubin Liang, Mohamad Bouhamdan, Xia Hou, Kezhong Zhang, Jun Song, Ke Hao, Jian-Ping Jin, Zhongyang Zhang, Jie Xu
Summary: The study identified a new CF animal model that exhibits intestinal dysbiosis phenotype, which may facilitate research and development of novel treatments for CF-associated gastrointestinal diseases. The fecal microbiomes of CF rabbits showed lower richness and diversity compared to wild-type rabbits, indicating significant taxonomic and functional dysbiosis.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Cell Biology
Airong Qian, Tzu-Bou Hsieh, M. Moazzem Hossain, Jim J-C Lin, J-P Jin
Summary: Calponin 2 is a crucial protein regulating cell motility-related functions and cell division. Proper expression levels and degradation of calponin 2 play essential roles in normal cytokinesis. PKC phosphorylation-triggered degradation of calponin 2 may determine the rate of cell division.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Monica Rasmussen, Han-Zhong Feng, J-P Jin
Summary: The troponin-based calcium regulation of muscle contraction emerged approximately 700 million years ago and has largely conserved functions during evolution. However, cardiac troponin I (TnI) in vertebrates has evolved specific muscle type-specific isoforms, including phosphorylation sites for beta-adrenergic regulation. This rapid evolution suggests a high selection value for vertebrate hearts to adapt to increased metabolic demands on land.
JOURNAL OF MOLECULAR EVOLUTION
(2022)
Review
Physiology
Monica Rasmussen, Jian-Ping Jin
Summary: The regulation of muscle contraction by troponin is essential for muscle quality, with specific isoforms expressed in different types of muscle fibers and adapted during development, aging, exercise, and disuse. Mutations in troponin subunits can lead to myopathies, making troponin variants useful markers for defining muscle quality and function. Understanding troponin modifications and mutants is crucial for improving human health by addressing age-related declines in muscle function and myopathies.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Cell Biology
Chad M. Warren, Monika Halas, Paul H. Goldspink, Han-Zhong Feng, Anthony W. Herren, Beata M. Wolska, Pieter P. de Tombe, Jian-Ping Jin, R. John Solaro
Summary: In this study, the impact of chronic expression of cTnI-ND in transgenic mouse hearts was investigated. It was found that the modification of cTnI-ND in the sarcomere initiates changes in the phosphorylation signaling pathways, which may be involved in the chronic-adaptive response to stressors.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2022)
Article
Physiology
Monica Rasmussen, Jian-Ping Jin
Summary: This study introduces a novel approach using monoclonal antibodies as molecular probes to detect and monitor conformational changes of troponin subunits. The effectiveness of this approach in assessing ligand-induced conformations of troponin subunits in physiological conditions is demonstrated through a comparison of high-throughput microplate assay and localized surface plasmon resonance. This method requires small amounts of protein and is free of protein modification.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tianxin Cao, Shirin Akhter, J-P Jin
Summary: Troponin T (TnT) is a key component of the troponin complex involved in regulating muscle contraction. It has evolved through alternative splicing to generate isoforms with muscle type-specific functions. The C-terminal region of TnT has a variable splicing segment that interfaces with other subunits and is important for its function. The evolution of TnT isoforms is associated with functional differences in muscle contraction.
JOURNAL OF MOLECULAR EVOLUTION
(2022)
Article
Physiology
Tzu-Bou Hsieh, Jian-Ping Jin
Summary: Deletion of calponin 2 exacerbates age-progressive degeneration of the glomerular structure and function as filtration barrier, suggesting a critical role of calponin 2 in podocytes and providing a new molecular target for understanding the pathogenesis of proteinuria and therapeutic development.
PHYSIOLOGICAL REPORTS
(2022)
Article
Physiology
Han-Zhong Feng, Xupei Huang, Jian-Ping Jin
Summary: This study demonstrates that restrictive deletion of the N-terminal extension of cardiac troponin I enhances the Frank-Starling response of the heart by increasing myofilament sensitivity to passive tension rather than relying on resting sarcomere length.
JOURNAL OF GENERAL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yuri Nagaoka, Kotone Oshiro, Yuta Yoshino, Toshiyuki Matsunaga, Satoshi Endo, Akira Ikari
Summary: This study investigated the effect of intercellular adhesion molecule CLDN1 on the anticancer drug sensitivity of small-cell lung cancer (SCLC) cells. It was found that overexpression of CLDN1 decreased the sensitivity of SCLC cells to anticancer drugs and enhanced their migratory capacity through the activation of the TGF-81/EMT signaling pathway. Treatment with EMT inhibitors showed potential in overcoming the reduced sensitivity to anticancer drugs in CLDN1-overexpressing SCLC cells.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2024)