Review
Biochemistry & Molecular Biology
Shiyu Luo, Samantha M. Rosen, Qifei Li, Pankaj B. Agrawal
Summary: Mutations in SPEG gene are associated with centronuclear myopathy, cardiomyopathy, or a combination of both, playing critical roles in skeletal and cardiac muscle development, maintenance, and function. Understanding the basic mechanisms of SPEG in regulating muscle development will provide insights into therapeutic targets for SPEG-related disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cardiac & Cardiovascular Systems
Hannah Campbell, Yuriana Aguilar-Sanchez, Ann P. Quick, Dobromir Dobrev, Xander H. T. Wehrens
Summary: Proper regulation of cardiac Ca2+ handling is crucial for normal excitation-contraction coupling, with SPEG playing a key role in maintaining this homeostasis and being implicated in various cardiovascular diseases.
CARDIOVASCULAR RESEARCH
(2021)
Review
Cardiac & Cardiovascular Systems
Hannah Campbell, Yuriana Aguilar-Sanchez, Ann P. Quick, Dobromir Dobrev, Xander H. T. Wehrens
Summary: Proper cardiac Ca2+ homeostasis is crucial for normal excitation-contraction coupling, and SPEG, as a key regulator in maintaining normal cardiac Ca2+ handling, plays a crucial role in both physiology and human disease processes, contributing to various genetic and acquired cardiovascular diseases.
CARDIOVASCULAR RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Yukari Endo, Linda Groom, Sabrina M. Wang, Emanuela Pannia, Nigel W. Griffiths, Jenica L. M. Van Gennip, Brian Ciruna, Jocelyn Laporte, Robert T. Dirksen, James J. Dowling
Summary: CACNA1S-related myopathy is a congenital muscle disease with no effective therapies available. The lack of suitable animal models has hindered its study. Researchers have successfully generated zebrafish models that mimic key aspects of the severe and mild forms of the disease, providing a basis for future mechanistic studies and therapy development.
HUMAN MOLECULAR GENETICS
(2023)
Article
Multidisciplinary Sciences
Alexandre Prola, Jordan Blondelle, Aymeline Vandestienne, Jerome Piquereau, Raphael G. P. Denis, Stephane Guyot, Hadrien Chauvin, Arnaud Mourier, Marie Maurer, Celine Henry, Nahed Khadhraoui, Cindy Gallerne, Thibaut Molinie, Guillaume Courtin, Laurent Guillaud, Melanie Gressette, Audrey Solgadi, Florent Dumont, Julien Castel, Julien Ternacle, Jean Demarquoy, Alexandra Malgoyre, Nathalie Koulmann, Genevieve Derumeaux, Marie-France Giraud, Frederic Joubert, Vladimir Veksler, Serge Luquet, Frederic Relaix, Laurent Tiret, Fanny Pilot-Storck
Summary: Mice deficient for a muscle-specific enzyme of very-long-chain fatty acid synthesis displayed increased basal energy expenditure and protection against high-fat diet-induced obesity. Muscle-specific modulation of the very-long-chain fatty acid pathway was associated with a reduced content of inner mitochondrial membrane phospholipid cardiolipin and a blunted coupling efficiency between the respiratory chain and ATP synthase, which was restored by cardiolipin enrichment. Selective increase of lipid oxidative capacities in skeletal muscle, through the cardiolipin-dependent lowering of mitochondrial ATP production, provides an effective option against obesity at the whole-body level.
Article
Clinical Neurology
Charlotte Gineste, Alix Simon, Marie Braun, David Reiss, Jocelyn Laporte
Summary: The study shows that tamoxifen can improve muscle function and structure in mouse models of BIN1 and DNM2-related centronuclear myopathies, likely by reducing dynamin 2 levels. This suggests the potential repurposing of tamoxifen for the treatment of autosomal forms of centronuclear myopathies.
Article
Clinical Neurology
Bungo Hirose, Kazuna Ikeda, Daisuke Yamamoto, Emiko Tsuda, Rika Yamauchi, Takayoshi Hozuki, Yoshiki Masuda, Tomihiro Imai
Summary: The study aimed to develop a simple and reliable technique for early diagnosis of critical illness myopathy (CIM) by evaluating excitation-contraction (E-C) coupling. The measurement of E-C coupling time (ECCT) was found to be an effective method to detect reduced muscle membrane excitability in the early stage of CIM.
CLINICAL NEUROPHYSIOLOGY
(2022)
Review
Pediatrics
Gang Zhang, Min Xu, Tingting Huang, Wenxin Lin, Jinglin Chen, Wangyang Chen, Xingzhi Chang
Summary: Centronuclear myopathy is a type of muscle disorder caused by mutations in the SPEG gene. This study reported a case of two sisters with compound heterozygous mutations in the SPEG gene, expanding the understanding of the disease.
Article
Medicine, Research & Experimental
Qifei Li, Jasmine Lin, Jeffrey J. Widrick, Shiyu Luo, Gu Li, Yuanfan Zhang, Jocelyn Laporte, Mark A. Perrella, Xiaoli Liu, Pankaj B. Agrawal
Summary: This study demonstrated that reducing DNM2 levels can improve the muscle phenotype in SPEG-deficient mice, but has no effect on cardiac dysfunction. Therefore, combining DNM2 reduction with other strategies may be necessary to target both the cardiac and skeletal defects associated with SPEG deficiency.
Article
Biochemistry & Molecular Biology
Cathrine Nordgaard, Anna Constance Vind, Amy Stonadge, Rasmus Kjobsted, Goda Snieckute, Pedro Antas, Melanie Blasius, Marie Sofie Reinert, Ana Martinez Del Val, Dorte Breinholdt Bekker-Jensen, Peter Haahr, Yekaterina A. Miroshnikova, Abdelghani Mazouzi, Sarah Falk, Emeline Perrier-Groult, Christopher Tiedje, Xiang Li, Jens Rithamer Jakobsen, Nicolas Oldenburg Jorgensen, Jorgen F. P. Wojtaszewski, Frederic Mallein-Gerin, Jesper Lovind Andersen, Cristian Pablo Pennisi, Christoffer Clemmensen, Moustapha Kassem, Abbas Jafari, Thijn Brummelkamp, Vivian S. W. Li, Sara A. Wickstrom, Jesper Velgaard Olsen, Gonzalo Blanco, Simon Bekker-Jensen
Summary: This study reveals the mechanisms by which muscle fibers sense mechanical load to activate p38 and JNK signaling. ZAK is able to recognize stress fibers in cells and Z-discs in muscle fibers under mechanical stress. ZAK deficiency leads to skeletal muscle defects and changes in myosin profile.
Article
Neurosciences
Valerie Biancalana, John Rendu, Annabelle Chaussenot, Helen Mecili, Eric Bieth, Melanie Fradin, Sandra Mercier, Maud Michaud, Marie-Christine Nougues, Laurent Pasquier, Sabrina Sacconi, Norma B. Romero, Pascale Marcorelles, Francois Jerome Authier, Antoinette Gelot Bernabe, Emmanuelle Uro-Coste, Claude Cances, Bertrand Isidor, Armelle Magot, Marie-Christine Minot-Myhie, Yann Pereon, Julie Perrier-Boeswillwald, Gilles Bretaudeau, Nicolas Dondaine, Alison Bouzenard, Megane Pizzimenti, Bruno Eymard, Ana Ferreiro, Jocelyn Laporte, Julien Faure, Johann Bohm
Summary: The recurrent RYR1 mutation previously classified as VUS was found in thirteen patients from nine unrelated congenital myopathy families with consistent clinical presentation, providing evidence of its pathogenicity. This mutation causes an atypical congenital myopathy with slowly improving motor function over the first decades of life, indicating a potential for directing molecular diagnosis for patients with similar clinical presentation.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Biology
Xueyong Wang, Murad Nawaz, Chris DuPont, Jessica H. Myers, Steve Ra Burke, Roger A. Bannister, Brent D. Foy, Andrew A. Voss, Mark M. Rich
Summary: Excitation-contraction coupling is the process of converting electrical excitation of muscle into force generation. Depolarization of skeletal muscle can lead to failure of ECC, specifically the failure to generate calcium transients. Different AP properties, such as AP peak and AP integral, play important roles in different steps of ECC, including AP conduction and calcium release.
Review
Physiology
Walter C. Thompson, Paul H. Goldspink
Summary: This review focuses on the crucial role of 14-3-3 proteins in regulating excitation-contraction coupling in muscle, highlighting the need for further investigation into their mechanistic actions in force generation.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2022)
Article
Cell Biology
Suzie Buono, Arnaud Monseur, Alexia Menuet, Anne Robe, Catherine Koch, Jocelyn Laporte, Leen Thielemans, Marion Depla, Belinda S. Cowling
Summary: Generating reliable preclinical data in animal models of disease is crucial for therapy development. In this study, statistical analysis and modeling were conducted to predict disease progression, which was then validated using data from a new colony of mice, demonstrating the reproducibility of disease phenotype. Furthermore, the refined phenotypic parameters were used to test the therapeutic efficacy of Dnm2 targeting, showing a significant improvement in disease progression.
DISEASE MODELS & MECHANISMS
(2022)
Article
Medicine, General & Internal
Narjara Castillo-Ferran, Juan Mario Junco-Rodriguez, Zurina Lestayo-O'Farrill, Maria de los Angeles Robinson-Agramonte, Zoilo Camejo-Leon, Hector Jesus Gomez-Suarez, Mercedes Salinas-Olivares, Evelyn Antiguas-Valdez, Elizabeth Falcon-Lamazares, Dario Siniscalco
Summary: Congenital myopathies (CMs) are a group of diseases characterized by muscle weakness and hypotonia. Centronuclear CM, characterized by centrally located nuclei in muscle fibers, was diagnosed in a 22-year-old male patient with muscle weakness since childhood. Neurogenic patterns were observed in electromyography and neuroconduction studies showed motor nerve involvement. The presence of fibers with central nuclei confirmed the diagnosis of CM. Understanding the pathological findings in CM is important for early treatment.
MEDICINA-LITHUANIA
(2023)
Article
Clinical Neurology
Tamar E. Sztal, Mo Zhao, Caitlin Williams, Viola Oorschot, Adam C. Parslow, Aminah Giousoh, Michaela Yuen, Thomas E. Hall, Adam Costin, Georg Ramm, Phillip I. Bird, Elisabeth M. Busch-Nentwich, Derek L. Stemple, Peter D. Currie, Sandra T. Cooper, Nigel G. Laing, Kristen J. Nowak, Robert J. Bryson-Richardson
ACTA NEUROPATHOLOGICA
(2015)
Article
Developmental Biology
Xin Lou, Jeffrey T. A. Burrows, Ian C. Scott
BMC DEVELOPMENTAL BIOLOGY
(2015)
Article
Multidisciplinary Sciences
Parveen Sharma, Cynthia Abbasi, Savo Lazic, Allen C. T. Teng, Dingyan Wang, Nicole Dubois, Vladimir Ignatchenko, Victoria Wong, Jun Liu, Toshiyuki Araki, Malte Tiburcy, Cameron Ackerley, Wolfram H. Zimmermann, Robert Hamilton, Yu Sun, Peter P. Liu, Gordon Keller, Igor Stagljar, Ian C. Scott, Thomas Kislinger, Anthony O. Gramolini
NATURE COMMUNICATIONS
(2015)
Article
Cell & Tissue Engineering
Jeffrey T. A. Burrows, Bret J. Pearson, Ian C. Scott
Article
Developmental Biology
Ashish R. Deshwar, John C. Onderisin, Anastasiia Aleksandrova, Xuefei Yuan, Jeffrey T. A. Burrows, Ian C. Scott
DEVELOPMENTAL BIOLOGY
(2016)
Article
Biology
Ashish R. Deshwar, Serene C. Chng, Lena Ho, Bruno Reversade, Ian C. Scott
Article
Developmental Biology
Dong Hu, Ian C. Scott, Fran Snider, Colleen Geary-Joo, Xiang Zhao, David G. Simmons, James C. Cross
DEVELOPMENTAL BIOLOGY
(2013)
Article
Biochemistry & Molecular Biology
Avnika A. Ruparelia, Mo Zhao, Peter D. Currie, Robert J. Bryson-Richardson
HUMAN MOLECULAR GENETICS
(2012)
Article
Developmental Biology
Natalie Gibb, Savo Lazic, Xuefei Yuan, Ashish R. Deshwar, Meaghan Leslie, Michael D. Wilson, Ian C. Scott
Article
Biochemistry & Molecular Biology
Mo Zhao, Lindsay Smith, Jonathan Volpatti, Lacramioara Fabian, James J. Dowling
HUMAN MOLECULAR GENETICS
(2019)
Article
Multidisciplinary Sciences
Mengyi Song, Xuefei Yuan, Claudia Racioppi, Meaghan Leslie, Nathan Stutt, Anastasiia Aleksandrova, Lionel Christiaen, Michael D. Wilson, Ian C. Scott
Summary: GATA4/5/6 transcription factors are crucial for heart development and regulate the transition from mesoderm to cardiac fate. Loss of Gata5/6 alters the population structure of mesendoderm-derived cells and leads to extensive changes in chromatin accessibility near cardiac and pharyngeal genes.
Article
Biochemical Research Methods
Shimon M. Rosenthal, Tvisha Misra, Hala Abdouni, Tess C. Branon, Alice Y. Ting, Ian C. Scott, Anne-Claude Gingras
Summary: Researchers adapted proximity labeling for protein discovery in zebrafish, developing in vivo TurbolD and mini-Turbo labeling techniques. By providing biotin directly in the egg water, they demonstrated successful biotinylation of prey proteins after 12 hours, enabling time-resolved analysis of development.
MOLECULAR & CELLULAR PROTEOMICS
(2021)
Article
Developmental Biology
Ningning Hou, Yuxi Yang, Ian C. Scott, Xin Lou
DEVELOPMENTAL BIOLOGY
(2017)