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Myomaker

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https://www.readbyqxmd.com/read/28860190/insights-into-the-localization-and-function-of-myomaker-during-myoblast-fusion
#1
Dilani G Gamage, Eugenia Leikina, Malgorzata E Quinn, Anthony Ratinov, Leonid V Chernomordik, Douglas P Millay
Multinucleated skeletal muscle fibers form through the fusion of myoblasts during development and regeneration. Previous studies identified myomaker (Tmem8c) as a muscle-specific membrane protein essential for fusion. However, the specific function of myomaker and how its function is regulated are unknown. To explore these questions, we first examined the cellular localization of endogenous myomaker. Two independent antibodies showed that while myomaker does localize to the plasma membrane in cultured myoblasts, the protein also resides in the Golgi and post-Golgi vesicles...
August 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28771574/acute-and-chronic-effects-of-exercise-on-mrna-expression-in-the-skeletal-muscle-of-two-mouse-models-of-peripheral-artery-disease
#2
Hiroki Nagase, Shuhei Yao, Shota Ikeda
Endurance exercise improves walking performance in patients with peripheral artery disease (PAD), which is characterized by skeletal muscle dysfunction caused by lower extremity ischemia. Although transcriptional analyses of exercise-induced changes in normal animals and healthy volunteers have been reported, no detailed study has explored exercise-induced alterations in gene expression in PAD animal models. Here, we determined the acute and chronic effects of exercise on mRNA expression in the skeletal muscles of two mouse models of PAD...
2017: PloS One
https://www.readbyqxmd.com/read/28681861/a-defect-in-myoblast-fusion-underlies-carey-fineman-ziter-syndrome
#3
Silvio Alessandro Di Gioia, Samantha Connors, Norisada Matsunami, Jessica Cannavino, Matthew F Rose, Nicole M Gilette, Pietro Artoni, Nara Lygia de Macena Sobreira, Wai-Man Chan, Bryn D Webb, Caroline D Robson, Long Cheng, Carol Van Ryzin, Andres Ramirez-Martinez, Payam Mohassel, Mark Leppert, Mary Beth Scholand, Christopher Grunseich, Carlos R Ferreira, Tyler Hartman, Ian M Hayes, Tim Morgan, David M Markie, Michela Fagiolini, Amy Swift, Peter S Chines, Carlos E Speck-Martins, Francis S Collins, Ethylin Wang Jabs, Carsten G Bönnemann, Eric N Olson, John C Carey, Stephen P Robertson, Irini Manoli, Elizabeth C Engle
Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function. We characterize MYMK-CFZS as a congenital myopathy with marked facial weakness and additional clinical and pathologic features that distinguish it from other congenital neuromuscular syndromes...
July 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28579197/mir-491-inhibits-skeletal-muscle-differentiation-through-targeting-myomaker
#4
Jian He, Fei Wang, Peng Zhang, Wenjiong Li, Jing Wang, Jinglong Li, Hongju Liu, Xiaoping Chen
The myogenesis of skeletal muscle has several stages, including satellite cell proliferation, differentiation, fusion and specific muscle formation. Recent studies have shown that myomaker, a muscle-specific transmembrane protein, was critical for myoblasts fusion. However, the regulatory mechanism of myomaker and its effects on myogenesis remain elusive. In this study, miR-491 was identified as a post-transcriptional regulator of myomaker, which binds specifically to its 3' untranslated region leading to its down-regulation...
July 1, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28569755/myomerger-induces-fusion-of-non-fusogenic-cells-and-is-required-for-skeletal-muscle-development
#5
Malgorzata E Quinn, Qingnian Goh, Mitsutoshi Kurosaka, Dilani G Gamage, Michael J Petrany, Vikram Prasad, Douglas P Millay
Despite the importance of cell fusion for mammalian development and physiology, the factors critical for this process remain to be fully defined, which has severely limited our ability to reconstitute cell fusion. Myomaker (Tmem8c) is a muscle-specific protein required for myoblast fusion. Expression of myomaker in fibroblasts drives their fusion with myoblasts, but not with other myomaker-expressing fibroblasts, highlighting the requirement of additional myoblast-derived factors for fusion. Here we show that Gm7325, which we name myomerger, induces the fusion of myomaker-expressing fibroblasts...
June 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28569745/the-microprotein-minion-controls-cell-fusion-and-muscle-formation
#6
Qiao Zhang, Ajay A Vashisht, Jason O'Rourke, Stéphane Y Corbel, Rita Moran, Angelica Romero, Loren Miraglia, Jia Zhang, Eric Durrant, Christian Schmedt, Srinath C Sampath, Srihari C Sampath
Although recent evidence has pointed to the existence of small open reading frame (smORF)-encoded microproteins in mammals, their function remains to be determined. Skeletal muscle development requires fusion of mononuclear progenitors to form multinucleated myotubes, a critical but poorly understood process. Here we report the identification of Minion (microprotein inducer of fusion), a smORF encoding an essential skeletal muscle specific microprotein. Myogenic progenitors lacking Minion differentiate normally but fail to form syncytial myotubes, and Minion-deficient mice die perinatally and demonstrate a marked reduction in fused muscle fibres...
June 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28386024/control-of-muscle-formation-by-the-fusogenic-micropeptide-myomixer
#7
Pengpeng Bi, Andres Ramirez-Martinez, Hui Li, Jessica Cannavino, John R McAnally, John M Shelton, Efrain Sánchez-Ortiz, Rhonda Bassel-Duby, Eric N Olson
Skeletal muscle formation occurs through fusion of myoblasts to form multinucleated myofibers. From a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) loss-of-function screen for genes required for myoblast fusion and myogenesis, we discovered an 84-amino acid muscle-specific peptide that we call Myomixer. Myomixer expression coincides with myoblast differentiation and is essential for fusion and skeletal muscle formation during embryogenesis. Myomixer localizes to the plasma membrane, where it promotes myoblast fusion and associates with Myomaker, a fusogenic membrane protein...
April 21, 2017: Science
https://www.readbyqxmd.com/read/28272491/ten-eleven-translocation-2-tet2-is-involved-in-myogenic-differentiation-of-skeletal-myoblast-cells-in-vitro
#8
Xia Zhong, Qian-Qian Wang, Jian-Wei Li, Yu-Mei Zhang, Xiao-Rong An, Jian Hou
Muscle cell differentiation is a complex process that is principally governed by related myogenic regulatory factors (MRFs). DNA methylation is considered to play an important role on the expression of MRF genes and on muscle cell differentiation. However, the roles of enzymes specifically in myogenesis are not fully understood. Here, we demonstrate that Tet2, a ten-eleven translocation (Tet) methylcytosine dioxygenase, exerts a role during skeletal myoblast differentiation. By using an immunostaining method, we found that the levels of 5-hydroxymethylcytosine (5-hmC) were much higher in differentiated myotubes than in undifferentiated C2C12 myoblasts...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28186492/requirement-of-myomaker-mediated-stem-cell-fusion-for-skeletal-muscle-hypertrophy
#9
Qingnian Goh, Douglas P Millay
Fusion of skeletal muscle stem/progenitor cells is required for proper development and regeneration, however the significance of this process during adult muscle hypertrophy has not been explored. In response to muscle overload after synergist ablation in mice, we show that myomaker, a muscle specific membrane protein essential for myoblast fusion, is activated mainly in muscle progenitors and not myofibers. We rendered muscle progenitors fusion-incompetent through genetic deletion of myomaker in muscle stem cells and observed a complete reduction of overload-induced hypertrophy...
February 10, 2017: ELife
https://www.readbyqxmd.com/read/28161523/myomaker-is-required-for-the-fusion-of-fast-twitch-myocytes-in-the-zebrafish-embryo
#10
Weibin Zhang, Sudipto Roy
During skeletal muscle development, myocytes aggregate and fuse to form multinucleated muscle fibers. Inhibition of myocyte fusion is thought to significantly derail the differentiation of functional muscle fibers. Despite the purported importance of fusion in myogenesis, in vivo studies of this process in vertebrates are rather limited. Myomaker, a multipass transmembrane protein, has been shown to be the first muscle-specific fusion protein essential for myocyte fusion in the mouse. We have generated loss-of-function alleles in zebrafish myomaker, and found that fusion of myocytes into syncytial fast-twitch muscles was significantly compromised...
March 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/27825107/in-vivo-myomaker-mediated-heterologous-fusion-and-nuclear-reprogramming
#11
Yasuyuki Mitani, Ronald J Vagnozzi, Douglas P Millay
Knowledge regarding cellular fusion and nuclear reprogramming may aid in cell therapy strategies for skeletal muscle diseases. An issue with cell therapy approaches to restore dystrophin expression in muscular dystrophy is obtaining a sufficient quantity of cells that normally fuse with muscle. Here we conferred fusogenic activity without transdifferentiation to multiple non-muscle cell types and tested dystrophin restoration in mouse models of muscular dystrophy. We previously demonstrated that myomaker, a skeletal muscle-specific transmembrane protein necessary for myoblast fusion, is sufficient to fuse 10T 1/2 fibroblasts to myoblasts in vitro...
January 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27155222/pias1-is-essential-for-erythroid-and-vascular-development-in-the-mouse-embryo
#12
Jerfiz D Constanzo, Mi Deng, Smita Rindhe, Ke-Jing Tang, Cheng-Cheng Zhang, Pier Paolo Scaglioni
The protein inhibitor of activated STAT-1 (PIAS1) is one of the few known SUMO E3 ligases. PIAS1 has been implicated in several biological processes including repression of innate immunity and DNA repair. However, PIAS1 function during development and tissue differentiation has not been studied. Here, we report that Pias1 is required for proper embryonic development. Approximately 90% of Pias1 null embryos die in utero between E10.5 and E12.5. We found significant apoptosis within the yolk sac (YS) blood vessels and concomitant loss of red blood cells (RBCs) resulting in profound anemia...
July 1, 2016: Developmental Biology
https://www.readbyqxmd.com/read/26858401/structure-function-analysis-of-myomaker-domains-required-for-myoblast-fusion
#13
Douglas P Millay, Dilani G Gamage, Malgorzata E Quinn, Yi-Li Min, Yasuyuki Mitani, Rhonda Bassel-Duby, Eric N Olson
During skeletal muscle development, myoblasts fuse to form multinucleated myofibers. Myomaker [Transmembrane protein 8c (TMEM8c)] is a muscle-specific protein that is essential for myoblast fusion and sufficient to promote fusion of fibroblasts with muscle cells; however, the structure and biochemical properties of this membrane protein have not been explored. Here, we used CRISPR/Cas9 mutagenesis to disrupt myomaker expression in the C2C12 muscle cell line, which resulted in complete blockade to fusion. To define the functional domains of myomaker required to direct fusion, we established a heterologous cell-cell fusion system, in which fibroblasts expressing mutant versions of myomaker were mixed with WT myoblasts...
February 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26597853/expression-of-nuclear-factor-of-activated-t-cells-nfat-and-downstream-muscle-specific-proteins-in-ground-squirrel-skeletal-and-heart-muscle-during-hibernation
#14
Yichi Zhang, Kenneth B Storey
The thirteen-lined ground squirrel (Ictidomys tridecemlineatus) undergoes remarkable adaptive changes during hibernation. Interestingly, skeletal muscle remodelling occurs during the torpor-arousal cycle of hibernation to prevent net muscle loss despite inactivity. Reversible cardiomyocyte hypertrophy occurs in cardiac muscle, allowing the heart to preserve cardiac output during hibernation, while avoiding chronic maladaptive hypertrophy post-hibernation. We propose that calcium signalling proteins [calcineurin (Cn), calmodulin (CaM), and calpain], the nuclear factor of activated T cell (NFAT) family of transcription factors, and the NFAT targets myoferlin and myomaker contribute significantly to adaptations taking place in skeletal and cardiac muscle during hibernation...
January 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/26540045/myomaker-regulated-by-myod-myog-and-mir-140-3p-promotes-chicken-myoblast-fusion
#15
Wen Luo, Erxin Li, Qinghua Nie, Xiquan Zhang
The fusion of myoblasts is an important step during skeletal muscle differentiation. A recent study in mice found that a transmembrane protein called Myomaker, which is specifically expressed in muscle, is critical for myoblast fusion. However, the cellular mechanism of its roles and the regulatory mechanism of its expression remain unclear. Chicken not only plays an important role in meat production but is also an ideal model organism for muscle development research. Here, we report that Myomaker is also essential for chicken myoblast fusion...
November 2, 2015: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/25085416/myomaker-is-essential-for-muscle-regeneration
#16
Douglas P Millay, Lillian B Sutherland, Rhonda Bassel-Duby, Eric N Olson
Regeneration of injured adult skeletal muscle involves fusion of activated satellite cells to form new myofibers. Myomaker is a muscle-specific membrane protein required for fusion of embryonic myoblasts, but its potential involvement in adult muscle regeneration has not been explored. We show that myogenic basic helix-loop-helix (bHLH) transcription factors induce myomaker expression in satellite cells during acute and chronic muscle regeneration. Moreover, genetic deletion of myomaker in adult satellite cells completely abolishes muscle regeneration, resulting in severe muscle destruction after injury...
August 1, 2014: Genes & Development
https://www.readbyqxmd.com/read/25078621/myomaker-mediates-fusion-of-fast-myocytes-in-zebrafish-embryos
#17
Aurélie Landemaine, Pierre-Yves Rescan, Jean-Charles Gabillard
Myomaker (also called Tmem8c), a new membrane activator of myocyte fusion was recently discovered in mice. Using whole mount in situ hybridization on zebrafish embryos at different stages of embryonic development, we show that myomaker is transiently expressed in fast myocytes forming the bulk of zebrafish myotome. Zebrafish embryos injected with morpholino targeted against myomaker were alive after yolk resorption and appeared morphologically normal, but they were unable to swim, even under effect of a tactile stimulation...
September 5, 2014: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/23868259/myomaker-is-a-membrane-activator-of-myoblast-fusion-and-muscle-formation
#18
Douglas P Millay, Jason R O'Rourke, Lillian B Sutherland, Svetlana Bezprozvannaya, John M Shelton, Rhonda Bassel-Duby, Eric N Olson
Fusion of myoblasts is essential for the formation of multi-nucleated muscle fibres. However, the identity of muscle-specific proteins that directly govern this fusion process in mammals has remained elusive. Here we identify a muscle-specific membrane protein, named myomaker, that controls myoblast fusion. Myomaker is expressed on the cell surface of myoblasts during fusion and is downregulated thereafter. Overexpression of myomaker in myoblasts markedly enhances fusion, and genetic disruption of myomaker in mice causes perinatal death due to an absence of multi-nucleated muscle fibres...
July 18, 2013: Nature
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