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)
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
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
Biochemistry & Molecular Biology
Kendal Prill, Michael R. Jones, Karl Steffensen, Grace Zi Teng, John F. Dawson
Summary: Many therapeutics for cardiomyopathy only alleviate symptoms without addressing the underlying mechanism. The onset of cardiomyopathy is believed to involve changes in calcium sensitivity and myosin activity. Trifluoperazine (TFP), a compound that binds troponin and other components of the calcium pathway, was studied to evaluate its impact on calcium regulation and heart function. In vitro experiments showed that TFP increased cardiac actomyosin activity while in vivo experiments using embryonic zebrafish demonstrated elevated heart rates with effective drug concentrations. In silico modeling suggested structural changes in troponin that could affect protein interactions within thin filaments and therefore impact heart function regulation.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Review
Biochemistry & Molecular Biology
Paul Dowling, Stephen Gargan, Dieter Swandulla, Kay Ohlendieck
Summary: The loss of skeletal muscle mass and strength is the main cause of frailty syndrome, which is closely associated with sarcopenia in the elderly. Mass spectrometry-based proteomic surveys have improved our understanding of the molecular and cellular changes during muscle atrophy and age-related fiber-type shifting. Proteomic analysis suggests that contractile proteins can be used as markers of fiber-type transitions during aging.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Islam M. Saadeldin, Hammed A. Tukur, Riyadh S. Aljumaah, Ramya A. Sindi
Summary: ROCK proteins play crucial roles in regulating cellular processes such as proliferation, adhesion, and differentiation. Inhibition of ROCKs can selectively switch cell fate, offering a novel approach for in vitro oocyte maturation, experimental embryology, and clinical applications.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
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
Engineering, Biomedical
Gyuhyung Jin, Martha E. Floy, Aaron D. Simmons, Madeline M. Arthur, Sean P. Palecek
Summary: This study introduces a simple and versatile method to spatially pattern differentiation of human pluripotent stem cells (hPSCs) in 2-dimensional culture via localized morphogen adsorption, allowing for induction of different cell types such as mesendoderm, endoderm, and cardiomyocytes. This approach provides a platform for controlled and systematic study of early pattern formation and can be used to generate 2D patterned hPSC-derived tissue structures for modeling disease and drug interactions.
ADVANCED HEALTHCARE MATERIALS
(2021)
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
Biochemical Research Methods
Prakhar Mishra, Ricky Cohen, Nanxia Zhao, Prabhas Moghe
Summary: This study explores the lack of robust methods to quickly discern the phenotypic and functional heterogeneity of stem cells, focusing on the organization of actin cytoskeleton to distinguish divergent stem cell differentiation pathways. By labeling actin filaments in live stem cells and studying their turnover dynamics, the researchers successfully demonstrated lineage specific changes in actin turnover during MSC differentiation and detected differences in actin dynamics during adipogenic or osteogenic differentiation. This method was also applied to differentiating iPSCs, showing a progressive slowdown in actin turnover during differentiation. Additionally, actin dynamic profiling was used to isolate MSCs into distinct sub-populations based on their actin dynamics, revealing correlations between actin dynamics and cell differentiation fates.
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
Biochemistry & Molecular Biology
William Lehman, Elumalai Pavadai, Michael J. Rynkiewicz
Summary: TnI interacts with tropomyosin to induce muscle relaxation under low-Ca2+ conditions and releases inhibition under high-Ca2+ conditions. Recent cryo-EM reconstructions have shown density attributed to TnI along cardiac muscle thin filaments at both low- and high-Ca2+ concentration.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Cell & Tissue Engineering
Lachlan Harris, Piero Rigo, Thomas Stiehl, Zachary B. Gaber, Sophie H. L. Austin, Maria del Mar Masdeu, Amelia Edwards, Noelia Urban, Anna Marciniak-Czochra, Francois Guillemot
Summary: The stabilization of neural stem cell numbers in young adults is a result of coordinated changes in stem cell behavior, with resting cells having a higher activation rate and greater contribution to neurogenesis. This change is associated with a progressive reduction in expression of the pro-activation protein ASCL1 due to increased post-translational degradation, providing insights into hippocampal NSC dynamics and neurogenesis rates in different mammalian species, including humans.
Article
Multidisciplinary Sciences
Jiro Usukura, Akihiro Narita, Tomoharu Matsumoto, Eiji Usukura, Takeshi Sunaoshi, Syunya Watanabe, Yusuke Tamba, Yasuhira Nagakubo, Takashi Mizuo, Junzo Azuma, Masako Osumi, Kazutaka Nimura, Ryuichiro Tamochi, Yoichi Ose
Summary: The new type of cryo-electron microscope allows simultaneous acquisition of transmission and surface images, with high-quality images at 30 kV. Using the unroofing method, fine structures near the cell membrane become visible, including the cytoskeleton, polyribosome chains, and endoplasmic reticulum.
SCIENTIFIC REPORTS
(2021)
Article
Cardiac & Cardiovascular Systems
Joaquim Grego-Bessa, Paula Gomez-Apinaniz, Belen Prados, Manuel Jose Gomez, Donal MacGrogan, Jose Luis de la Pompa
Summary: This study investigated the functions and downstream mechanisms of Nrg1 signaling during ventricular chamber development. The Nrg1-ErbB2/ErbB4-Erk axis was found to be a crucial regulator of cardiomyocyte cell cycle progression and migration.
CIRCULATION RESEARCH
(2023)
Article
Cell Biology
Yun Shi, Julia P. Bethea, Hannah L. Hetzel-Ebben, Maicon Landim-Vieira, Ross J. Mayper, Regan L. Williams, Lauren E. Kessler, Amanda M. Ruiz, Kathryn Gargiulo, Jennifer S. M. Rose, Grayson Platt, Jose R. Pinto, Brian K. Washburn, P. Bryant Chase
Summary: The study on the mandibular muscle structure and function of major workers of the Florida carpenter ant revealed features that explain the rightward shift of calcium activation and structural implications for the troponin complex. This sheds light on how mandibular muscle fibers perform various functions and the role of troponin in these tasks.
JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY
(2021)
Article
Cell Biology
Michael L. Rossetti, Kirsten R. Dunlap, Gloria Salazar, Robert C. Hickner, Jeong-Su Kim, Bryant P. Chase, Benjamin F. Miller, Bradley S. Gordon
Summary: Decreased testicular androgen production leads to muscle mass loss, and a mitochondria targeted antioxidant may help preserve limb muscle mass.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Biology
Maicon Landim-Vieira, Matthew C. Childers, Amanda L. Wacker, Michelle Rodriquez Garcia, Huan He, Rakesh Singh, Elizabeth A. Brundage, Jamie R. Johnston, Bryan A. Whitson, P. Bryant Chase, Paul M. L. Janssen, Michael Regnier, Brandon J. Biesiadecki, J. Renato Pinto, Michelle S. Parvatiyar
Summary: In this study, we identified novel post-translational modifications (PTMs) on beta-myosin heavy chain (beta-MHC) in normal and failing human heart tissues using proteomics and quantification methods. These PTMs, including acetylation and phosphorylation, were found to play crucial roles in regulating myocardial contractility. Our findings suggest that the location of PTMs on beta-MHC may have a greater impact on their acetylation levels than the type of heart disease. Furthermore, these modifications have the potential to modulate various cellular processes and protein interactions involved in cardiac muscle contraction.
Article
Physiology
Kirsten R. R. Dunlap, Jennifer L. L. Steiner, Robert C. C. Hickner, P. Bryant Chase, Bradley S. S. Gordon
Summary: Glucocorticoids induce muscle myopathy, but resistance exercise can reverse muscle loss by promoting muscle protein synthesis. However, it is unclear whether resistance exercise can induce an anabolic response in glucocorticoid myopathic muscle, which may be due to altered gene expression caused by long-term glucocorticoid exposure. This study aimed to assess whether high-force contractions can initiate an anabolic response in glucocorticoid myopathic muscle.
JOURNAL OF APPLIED PHYSIOLOGY
(2023)
Editorial Material
Physiology
P. Bryant Chase, Arianna N. Coons
Review
Biochemistry & Molecular Biology
Isabella Leite Coscarella, Maicon Landim-Vieira, Hosna Rastegarpouyani, Prescott Bryant Chase, Jerome Irianto, Jose Renato Pinto
Summary: Cardiac muscle contraction is different from other muscle types, with the heart continuously undergoing contraction-relaxation cycles. Mechanotransduction in the cardiomyocyte involves the transmission of mechanical signals to the nucleus, leading to changes in gene expression and nucleus morphology. Understanding the correlation between nucleus sensing and dysfunction of sarcomeric proteins may help in studying cardiomyopathic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Michelle Rodriguez Garcia, Jeffrey Schmeckpeper, Maicon Landim-Vieira, Isabella Leite Coscarella, Xuan Fang, Weikang Ma, Payton A. Spran, Shengyao Yuan, Lin Qi, Aida Rahimi Kahmini, M. Benjamin Shoemaker, James B. Atkinson, Peter M. Kekenes-Huskey, Thomas C. Irving, Prescott Bryant Chase, Bjoern C. Knollmann, Jose Renato Pinto
Summary: In this study, the effects of an ACTN2 missense variant (p.A868T) on cardiac muscle structure and function were investigated. The results showed small structural changes in cardiomyocytes at the ultrastructural level, as well as increased myofilament Ca-2+ sensitivity and faster rates of tension redevelopment in the ACTN2 A868T variant cardiac tissue. Molecular dynamics simulations suggested that the mutation may alter the conformation associated with titin binding. This study establishes the role of alpha-actinin 2 in modulating cross-bridge kinetics and force development in the human myocardium, and provides insights into its involvement in the development of cardiac disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Biophysics
Maicon Landim-Vieira, Weikang Ma, Taejeong Song, Coen A. Ottenheijm, Hyun S. Hwang, Henry M. Gong, Maria Papadaki, Bjorn C. Knollmann, Sakthivel Sadayappan, Thomas C. Irving, Prescott B. Chase, J. Renato Pinto
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Isabella Leite Coscarella, Lili Wang, Jerome Irianto, Bjorn C. Knollmann, Prescott B. Chase, J. Renato Pinto
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Michelle C. Rodriguez Garcia, Maicon Landim-Vieira, Jeffrey Schmeckpeper, Lili Wang, Moore B. Shoemaker, Prescott B. Chase, Bjorn C. Knollmann, J. Renato Pinto
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Cristina M. Risi, Betty Belknap, Maicon Landim-Vieira, Kelly A. Dryden, Howard D. White, Jose R. Pinto, P. Bryant Chase, Vitold E. Galkin
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Yun Shi, Linda Stroud, Vincent A. LaBarbera, Quinton R. Sparrow, Fang Wang, Lauren E. Kessler, Brenda Schoffstall, Prescott B. Chase
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Henry G. Zot, Prescott B. Chase, Javier E. Hasbun, J. Renato D. Pinto
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
Maicon Landim-Vieira, Weikang Ma, Taejeong Song, Coen Ottenheijm, Hyun Hwang, Bjorn C. Knollmann, Sakthivel Sadayappan, Thomas Irving, P. Bryant Chase, Jose Pinto
CIRCULATION RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Mayra A. Marques, Maicon Landim-Vieira, Adolfo H. Moraes, Bin Sun, Jamie R. Johnston, Karissa M. Dieseldorff Jones, Elio A. Cino, Michelle S. Parvatiyar, Isela C. Valera, Jerson L. Silva, Vitold E. Galkin, P. Bryant Chase, Peter M. Kekenes-Huskey, Guilherme A. P. de Oliveira, Jose Renato Pinto
Summary: This study elucidates the molecular mechanism of a human mutation in cardiac Troponin C and demonstrates its impact on sarcomere function and cardiomyopathy in transgenic mice. The findings suggest that disruption of molecular networks by protein mutations may compromise contractile performance and lead to cardiac diseases.