Article
Multidisciplinary Sciences
Carlo Manno, Eshwar Tammineni, Lourdes Figueroa, Isabelle Marty, Eduardo Rios
Summary: Triadin plays a key role in regulating calcium signaling and muscle function. Its knockout leads to alterations in calcium balance and changes in the expression of important proteins, such as calsequestrin. However, the muscle cells are able to compensate for these changes and maintain normal muscle function.
Article
Physiology
Colline Sanchez, Christine Berthier, Yves Tourneur, Laloe Monteiro, Bruno Allard, Laszlo Csernoch, Vincent Jacquemond
Summary: The study utilized a Ca2+-sensitive probe targeted to the junctional SR membrane of intact muscle fibers to investigate the functional properties of RYR-mediated SR Ca2+ release. Results showed spatial gradients of Ca2+ release and remarkable synchronicity of voltage-dependent Ca2+ release activation among individual triads, highlighting the potential of the approach to visualize activation or closure of single groups of RYR channels.
JOURNAL OF GENERAL PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Yukari Endo, Linda Groom, Alper Celik, Natalia Kraeva, Chang Seok Lee, Sung Yun Jung, Lois Gardner, Marie-Anne Shaw, Susan L. Hamilton, Philip M. Hopkins, Robert T. Dirksen, Sheila Riazi, James J. Dowling
Summary: This study identified rare variants in the ASPH gene as a new cause of susceptibility to exertional heat illness and malignant hyperthermia. The findings were validated using animal and cell models.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Sageanne Senneff, Madeleine M. Lowery
Summary: A computational model was presented to explore the effects of elevated extracellular potassium on force generation in muscle fibers. The model captured experimental observations of frequency-dependent force response to potassium accumulation, indicating that altered calcium release and phosphate accumulation work together with elevated potassium to affect force production during sustained contractions.
JOURNAL OF THEORETICAL BIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Jinhong Wei, Wenting Guo, Ruiwu Wang, John Paul Estillore, Darrell Belke, Yong-Xiang Chen, Alexander Vallmitjana, Raul Benitez, Leif Hove-Madsen, S. R. Wayne Chen
Summary: The physiological significance of PKA phosphorylation of RyR2 in the heart is still poorly understood. Recent structural studies have shown that the PKA phosphorylation site S2030 in RyR2 is located within a pathway that is important for the termination of Ca2+ release. We investigated the impact of S2030 mutations on Ca2+ release termination in cells and generated a mouse model to study the role of S2030 in a physiological setting.
CIRCULATION RESEARCH
(2023)
Article
Cell Biology
Sou Inagaki, Yoshiaki Suzuki, Keisuke Kawasaki, Rubii Kondo, Yuji Imaizumi, Hisao Yamamura
Summary: In this study, the role of mitochondrial fusion protein 2 (Mfn2) in the coupling of sarcoplasmic reticulum (SR) and mitochondria in vascular smooth muscle cells (VSMCs) was examined. It was found that Mfn2 is responsible for tethering mitochondria to SR, which regulates calcium signaling, ATP production, and cell proliferation in VSMCs.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Cedric R. Lamboley, Luke Pearce, Crystal Seng, Aldo Meizoso-Huesca, Daniel P. Singh, Barnaby P. Frankish, Vikas Kaura, Harriet P. Lo, Charles Ferguson, Paul D. Allen, Philip M. Hopkins, Robert G. Parton, Robyn M. Murphy, Chris van der Poel, Christopher J. Barclay, Bradley S. Launikonis
Summary: The study reveals that RyR1 Ca2+ leak causes redistribution of Ca2+ among different cellular structures by altering the Ca2+ permeability of different membranes, impacting muscle function. Individuals with gain-of-function RYR1 mutations may experience reduced force generation and increased susceptibility to MH.
Article
Biochemistry & Molecular Biology
Rizwan Qaisar, Gavin Pharaoh, Shylesh Bhaskaran, Hongyang Xu, Rojina Ranjit, Jan Bian, Bumsoo Ahn, Constantin Georgescu, Jonathan D. Wren, Holly Van Remmen
Summary: The study showed that pharmacological activation of SERCA can mitigate sarcopenia phenotype in aging mice, reversing reductions in muscle mass and force generation, and preventing an increase in mitochondrial ROS production. These effects are mediated in part by enhanced cellular energetics through activation of PGC1-alpha, UCP1, HSF1, and APMK, as well as increased regenerative capacity by suppression of MEF2C and p38 MAPK signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Takuya Kobayashi, Akihisa Tsutsumi, Nagomi Kurebayashi, Kei Saito, Masami Kodama, Takashi Sakurai, Masahide Kikkawa, Takashi Murayama, Haruo Ogawa
Summary: This study reveals the gating mechanism of RyR2 and how it is altered by pathogenic mutations through high-resolution structures and functional analysis.
NATURE COMMUNICATIONS
(2022)
Article
Endocrinology & Metabolism
Patrick A. Fletcher, Ben Thompson, Chante Liu, Richard Bertram, Leslie S. Satin, Arthur S. Sherman
Summary: The standard model for Ca2+ oscillations in insulin-secreting pancreatic 13 cells relies on voltage-activated Ca2+ channels for Ca2+ entry. These channels work together with ATP-dependent K+ channels to regulate the secretion of insulin in response to the metabolic state of the cells. However, an alternative model proposes that calcium-induced calcium release from the endoplasmic reticulum is the key driver of islet oscillations. This study shows that the alternative model is incompatible with established experimental data and that the standard model provides a better explanation for the new observations.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Biochemical Research Methods
Lyudmyla Borysova, Y. Y. Hanson Ng, Edward S. Wragg, Lillian E. Wallis, Emily Fay, Raimondo Ascione, Kim A. Dora
Summary: This protocol details how to conduct high spatial and temporal Ca2+ imaging of ex vivo multicellular myocardial strips, including the endocardial surface, to study the Ca2+ signaling that underpins cardiomyocyte contraction.
Article
Cell Biology
Marino DiFranco, Stephen C. Cannon
Summary: Hypokalemic periodic paralysis (HypoPP) is a skeletal muscle channelopathy caused by mutations in voltage sensor domains of calcium or sodium channels. Recurrent attacks of weakness are the primary clinical manifestation, resulting from impaired excitability of depolarized fibers containing leaky mutant channels. Reduced Ca2+-release in Ca(V)1.1 mutant channels may contribute to the late-onset permanent muscle weakness in Ca(V)1.1-associated HypoPP. The episodes of transient weakness in both Ca(V)1.1 and Na(V)1.4-associated HypoPP are primarily caused by leaky channels and are not a consequence of reduced Ca2+-release.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Zheng Fang Yang, Pankaj Panwar, Ciaran R. McFarlane, Wietske E. Tuinte, Marta Campiglio, Filip Van Petegem
Summary: Junctophilins (JPH) are proteins that connect the plasma membrane and the endoplasmic or sarcoplasmic reticulum, facilitating communication between proteins in different membranes. This study presents crystal structures of two JPH isoforms, revealing their importance in muscle excitation-contraction coupling. Various mutations in JPH2 and the L-type calcium channel affect their interaction and have been linked to cardiomyopathy and cardiac arrhythmia, respectively.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Physiology
Hiroaki Eshima
Summary: Obesity and diabetes can disrupt peripheral insulin resistance in skeletal muscle and lead to loss of muscle size, strength, and physical function, with contractile dysfunction being linked to impaired intracellular Ca2+ concentration regulation. Recent studies have shown that metabolic disorders affect interactions between the SR and mitochondrial networks, altering Ca2+ handling by these organelles. This review highlights the importance of understanding the impact of metabolic disorders on calcium regulation in skeletal muscle for potential therapeutic strategies.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Zsuzsanna E. Magyar, Judit Hevesi, Linda Groom, Robert T. Dirksen, Janos Almassy
Summary: The T4706M mutation in the RyR1 protein is associated with muscle weakness and alters channel function, leading to a complex mechanism of disease pathogenesis.
SCIENTIFIC REPORTS
(2023)
Article
Medicine, Research & Experimental
Loredana Migliore, Federico Galvagni, Enrico Pierantozzi, Vincenzo Sorrentino, Daniela Rossi
Summary: This study investigates the use of ASP-RNAi as a strategy to silence mutant alleles in TNNT2, a sarcomere protein associated with hypertrophic and dilated cardiomyopathy. Through experimental validation, different siRNAs were shown to effectively knockdown the mutant alleles. This research provides a foundation for the application of allele silencing as a therapeutic treatment for TNNT2-mutation-associated cardiomyopathies.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Enrico Pierantozzi, Peter Szentesi, Cecilia Paolini, Beatrix Dienes, Janos Fodor, Tamas Olah, Barbara Colombini, Dilson E. Rassier, Egidio Maria Rubino, Stephan Lange, Daniela Rossi, Laszlo Csernoch, Maria Angela Bagni, Carlo Reggiani, Vincenzo Sorrentino
Summary: Obscurin plays a significant role in skeletal muscle fibers, affecting muscle function and intracellular Ca2+ dynamics. The diaphragm of Obscn KO mice show prolonged TTP and HRT, decreased sarcoplasmic reticulum Ca2+ release and SERCA reuptake rates, as well as fiber damage, altered sarcomere ultrastructure and M-band disarray after intense exercise.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Daniela Rossi, Stefania Lorenzini, Enrico Pierantozzi, Filip Van Petegem, David Osamwonuyi Amadsun, Vincenzo Sorrentino
Summary: Junctin is a transmembrane protein that plays a role in striated muscles by interacting with calsequestrin and the ryanodine receptor. Our study found that junctin and calsequestrin co-localize in the endoplasmic reticulum and triads, and identified specific regions of junctin that can bind calsequestrin and the RyR. Deletion of these regions affects junctin's localization at the junctional SR.
JOURNAL OF CELL SCIENCE
(2022)
Article
Genetics & Heredity
Pauline Le Tanno, Xenia Latypova, John Rendu, Julien Faure, Veronique Bourg, Marjolaine Gauthier, Gipsy Billy-Lopez, Pierre-Simon Jouk, Klaus Dieterich
Summary: The study aimed to establish diagnostic recommendations for arthrogryposis multiplex congenita (AMC) using a nationwide cohort of children with AMC and literature data. A two-stage diagnostic process is recommended, including non-invasive investigations for classification and targeted investigations for specific patients.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Nutrition & Dietetics
Sarah Oddoux, Paul Violette, Jeanne Cornet, Julie Akkoyun-Farinez, Michel Besnier, Antoine Noel, Frederic Rouillon
Summary: Anxiety is a common psychological disorder that is often treated with benzodiazepines. However, these drugs have side effects and can lead to dependence. In this study, a dietary supplement was evaluated as an alternative treatment for anxiety, and it was found to be effective in reducing symptoms with minimal side effects.
Article
Pharmacology & Pharmacy
Isabelle Marty, Mathilde Beaufils, Julien Faure, John Rendu
Summary: Myopathies associated with RYR1 gene variations are genetic disorders with limited treatment options. The large size and wide distribution of variations along the sequence make it challenging to develop effective therapies. However, advancements in gene therapy and gene editing tools provide potential solutions at the mRNA and DNA levels. Promising results have been obtained in in vitro and in vivo studies, and inspiration can be drawn from other genetic diseases for the development of novel gene editing techniques.
CURRENT OPINION IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Feliciano Protasi, Barbara Girolami, Sara Roccabianca, Daniela Rossi
Summary: Store-Operated Ca2+ entry (SOCE) is an important mechanism in muscle physiology, responsible for refilling intracellular Ca2+ stores during muscle activity. The recent discovery of Ca2+ Entry Units (CEUs) in exercised muscle fibres provides new insights into the role of extracellular Ca2+ in muscle contraction and intracellular Ca2+ homeostasis. Mutations in proteins involved in SOCE have been linked to tubular aggregate myopathy, highlighting the importance of understanding the molecular pathways of Ca2+ entry for developing effective therapies.
CURRENT OPINION IN PHARMACOLOGY
(2023)
Article
Cell Biology
Laurence Serre, Julie Delaroche, Angelique Vinit, Guy Schoehn, Eric Denarier, Anne Fourest-Lieuvin, Isabelle Arnal
Summary: Adenomatous polyposis coli (APC), a scaffold protein with tumor suppressor properties, plays important roles in mitosis and cytoskeleton regulation. This study investigated the molecular mechanisms of APC-C, the C-terminal domain of APC, in microtubule regulation. It was found that APC-C promotes both microtubule growth and shrinkage and accumulates at shrinking microtubule extremities. Cryo-electron microscopy revealed that APC-C adopts an extended conformation along the protofilament crest and decorates microtubules with ring-like tubulin oligomers. Furthermore, APC-C's interaction with microtubules is essential for correct mitotic chromosome alignment. These findings suggest that the bilateral interaction of APC-C with tubulin and microtubules contributes to its mitotic functions.
JOURNAL OF CELL SCIENCE
(2023)
Article
Multidisciplinary Sciences
Alexis Osseni, Aymeric Ravel-Chapuis, Edwige Belotti, Isabella Scionti, Yann-Gael Gangloff, Vincent Moncollin, Laetitia Mazelin, Remi Mounier, Pascal Leblanc, Bernard J. Jasmin, Laurent Schaeffer
Summary: Authors demonstrate that inhibiting HDAC6 and promoting Smad3 acetylation can reverse Duchenne muscular dystrophy-like symptoms in mdx mice, pointing to HDAC6 as a potential therapeutic target for the disorder.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Clinical Neurology
Juliette Svahn, Laurent Coudert, Nathalie Streichenberger, Alexandra Kraut, Alice Gravier-Dumonceau-Mazelier, Ludivine Rotard, Laurence Calemard-Michel, Rita Menassa, Elisabeth Errazuriz-Cerda, Lara Chalabreysse, Alexis Osseni, Christophe Vial, Laurentiu Jomir, Francois Tronc, Do Le Duy, Emilien Bernard, Vincent Gache, Yohann Coute, Vincent Jacquemond, Laurent Schaeffer, Pascal Leblanc
Summary: This study reports a case of acquired autoimmune rippling muscle disease (iRMD) associated with thymoma and AchR antibody negativity. The patient was found to have circulating MURC/Cavin-4 autoantibodies, and the histological features of the patient's muscles were similar to those commonly reported in caveolinopathies. After tumor resection and immunotherapy, the levels of autoantibodies significantly decreased, the rippling phenotype disappeared completely, and the patient achieved full remission. Therefore, MURC/Cavin-4 autoantibodies may play a pathogenic role in the development of paraneoplastic iRMD associated with thymoma.
NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
(2023)
Article
Clinical Neurology
Afshin Saffari, Tracy Lau, Homa Tajsharghi, Ehsan Ghayoor Karimiani, Ariana Kariminejad, Stephanie Efthymiou, Giovanni Zifarelli, Tipu Sultan, Mehran Beiraghi Toosi, Sahar Sedighzadeh, Victoria Mok Siu, Juan Dario Ortigoza-Escobar, Aisha M. AlShamsi, Shahnaz Ibrahim, Nouriya Abbas Al-Sannaa, Walla Al-Hertani, Whalen Sandra, Mark Tarnopolsky, Shahryar Alavi, Chumei Li, Debra-Lynn Day-Salvatore, Maria Jesus Martinez-Gonzalez, Kristin M. Levandoski, Emma Bedoukian, Suneeta Madan-Khetarpal, Michaela J. Idleburg, Minal Juliet Menezes, Aishwarya Siddharth, Konrad Platzer, Henry Oppermann, Martin Smitka, Felicity Collins, Monkol Lek, Mohmmad Shahrooei, Maryam Ghavideldarestani, Isabella Herman, John Rendu, Julien Faure, Janice Baker, Vikas Bhambhani, Laurel Calderwood, Javad Akhondian, Shima Imannezhad, Hanieh Sadat Mirzadeh, Narges Hashemi, Mohammad Doosti, Mojtaba Safi, Najmeh Ahangari, Paria Najarzadeh Torbati, Soheila Abedini, Vincenzo Salpietro, Elif Yilmaz Gulec, Safieh Eshaghian, Mohammadreza Ghazavi, Michael T. Pascher, Marina Vogel, Angela Abicht, Sebastien Moutton, Ange-Line Bruel, Claudine Rieubland, Sabina Gallati, Tim M. Strom, Hanns Lochmueller, Mohammad Hasan Mohammadi, Javeria Raza Alvi, Elaine H. Zackai, Beth A. Keena, Cara M. Skraban, Seth Berger, Erin H. Andrew, Elham Rahimian, Michelle M. Morrow, Ingrid M. Wentzensen, Francisca Millan, Lindsay B. Henderson, Hormos Salimi Dafsari, Heinz Jungbluth, Natalia Gomez-Ospina, Anne McRae, Merlene Peter, Danai Veltra, Nikolaos M. Marinakis, Christalena Sofocleous, Farah Ashrafzadeh, Davut Pehlivan, Johannes R. Lemke, Judith Melki, Audrey Benezit, Peter Bauer, Denisa Weis, James R. Lupski, Jan Senderek, John Christodoulou, Wendy K. Chung, Rose Goodchild, Amaka C. Offiah, Andres Moreno-De-Luca, Mohnish Suri, Darius Ebrahimi-Fakhari, Henry Houlden, Reza Maroofian
Summary: This study systematically assesses the characteristics of 56 individuals with autosomal-recessive TOR1A-related disease, including their clinical, radiological, and molecular features. The study defines the phenotypic spectrum, identifies core clinical symptoms, and highlights predictors for disease severity and survival.
Article
Biochemistry & Molecular Biology
Ludovic D. D. Langlois, Sarah Oddoux, Kanhia Auble, Paul Violette, Pierre Dechelotte, Antoine Noel, Moise Coeffier
Summary: This study tested a new treatment approach for irritable bowel syndrome (IBS), which is known to be associated with increased intestinal permeability and inflammation. The results showed that a combination of glutamine, curcumin, polyunsaturated fatty acids, fish protein hydrolysate, and probiotics significantly reduced colonic hyperpermeability and inflammatory markers in a stress-based model of IBS. This has important implications for patients suffering from IBS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
E. Pierantozzi, L. Raucci, S. Buonocore, E. M. Rubino, Q. Ding, A. Laurino, F. Fiore, M. Soldaini, J. Chen, D. Rossi, P. Vangheluwe, H. Chen, V. Sorrentino
Summary: Genome-wide association studies and cis-expression quantitative trait locus analyses identified an association between the rs508419 SNP and type 2 diabetes. Functional studies showed that the C/C variant of rs508419 increases the activity of the P2 promoter, leading to higher levels of sAnk1.5 expression. However, overexpression of sAnk1.5 in skeletal muscle does not predispose mice to susceptibility to type 2 diabetes.
SCIENTIFIC REPORTS
(2023)
Article
Genetics & Heredity
Ivana Dabaj, Robert Y. Carlier, Klaus Dieterich, Isabelle Desguerre, Julien Faure, Norma B. Romero, Wenting Trang, Susana Quijano-Roy, Dominique P. Germain
Summary: Sheldon-Hall syndrome (SHS) is a rare congenital contracture syndrome caused by pathogenic variants in genes encoding the fast-twitch skeletal muscle contractile myofiber complex. This study reports the association between a pathogenic variant in the TNNT3 gene and neurogenic features in a patient with SHS. Further research is needed to investigate the developmental abnormalities that may lead to pseudo-neurogenic EMG features.
FRONTIERS IN GENETICS
(2023)
Article
Biology
Alexis Osseni, Jean-Luc Thomas, Alireza Ghasemizadeh, Laurent Schaeffer, Vincent Gache
Summary: An efficient communication between nerve and muscle at the neuromuscular junctions is essential for movement and breathing. Understanding the adaptation of the neuromuscular system to denervation is crucial for studying neuromuscular diseases. Currently, there is a lack of in vitro models that fully replicate the in vivo situation, making in vivo denervation an important method for studying adaptation to denervation.