scholarly journals Myomerger induces fusion of non-fusogenic cells and is required for myoblast fusion

2017 ◽  
Author(s):  
Malgorzata E. Quinn ◽  
Qingnian Goh ◽  
Mitsutoshi Kurosaka ◽  
Dilani G. Gamage ◽  
Michael J. Petrany ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Fusion ◽  
Specific Protein ◽  
Myoblast Fusion ◽  
Mammalian Development ◽  
Normal Muscle ◽  
Muscle Formation ◽  
Biochemical Mechanisms ◽  
Genetic Deletion ◽  
Myoblast Cell

AbstractDespite the importance of cell fusion for mammalian development and physiology, the factors critical for this process remain to be fully defined1. This lack of knowledge has severely limited our ability to reconstitute cell fusion, which is necessary to decipher the biochemical mechanisms driving plasma membrane merger. Myomaker (Tmem8c) is a muscle-specific protein required for myoblast fusion2,3. Expression of myomaker in fibroblasts drives their fusion with myoblasts, but not with other myomaker-fibroblasts, highlighting the requirement of additional myoblast-derived factors for fusion. Here, we demonstrate that Gm7325, named myomerger, induces the fusion of myomaker-expressing fibroblasts. Cell mixing experiments reveal that while myomaker renders cells fusion-competent, myomerger induces fusogenicity. Thus, myomaker and myomerger confer fusogenic activity to normally non-fusogenic cells. Myomerger is skeletal muscle-specific and only expressed during developmental and regenerative myogenesis. Disruption of myomerger in myoblast cell lines through Cas9-mutagenesis generated non-fusogenic myocytes. Genetic deletion of myomerger in mice results in a paucity of muscle fibers demonstrating a requirement for myomerger in normal muscle formation. Myomerger deficient myocytes exhibit an ability to differentiate and harbor organized sarcomeres, however remain mono-nucleated. These data identify myomerger as a fundamental myoblast fusion protein and establishes a system that begins to reconstitute mammalian cell fusion.

scholarly journals Signaling mechanism of myoblast fusion in skeletal muscle formation

2019 ◽  
Vol 92 (0) ◽  
pp. 1-S04-4
Author(s):  
Taichiro Tomida ◽  
Kimitaka Yamaguchi ◽  
Masanori Ito ◽  
Yoshinori Mikami ◽  
Daisuke Ohshima ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Myoblast Fusion ◽  
Signaling Mechanism ◽  
Muscle Formation ◽  
Skeletal Muscle Formation

Actin regulators take the reins in Drosophila myoblast fusion

2009 ◽  
Vol 4 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Susanne-Filiz Önel
Keyword(s):  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Myoblast Fusion ◽  
Fusion Pore ◽  
Specific Cell ◽  
Muscle Formation ◽  
Biochemical Analyses ◽  
Made In ◽  
Skeletal Muscle Formation

AbstractSkeletal muscle formation, growth and repair depend on myoblast fusion events. Therefore, in-depth understanding of the underlying molecular mechanisms controlling these events that ultimately lead to skeletal muscle formation may be fundamental for developing new therapies for tissue repair. To this end, the greatest advances in furthering understanding myoblast fusion has been made in Drosophila. Recent studies have shown that transient F-actin structures, so-called actin plugs or foci, are known to form at the site of contacting myoblasts. Indeed, actin regulators of the WASP family that control the activation of the Arp2/3 complex and thereby branched F-actin formation have been demonstrated to be crucial for myoblast fusion. Myoblast-specific cell adhesion molecules seem to be involved in the recruitment of WASP family members to the site of myoblast fusion and form a Fusion-Restricted Myogenic-Adhesive Structure (FuRMAS). Currently, the exact role of the FuRMAS is not completely understood. However, recent studies indicate that WASP-dependent F-actin regulation is required for fusion pore formation as well as for the correct integration of fusing myoblasts into the growing muscle. In this review, I discuss latest cellular studies, and recent genetic and biochemical analyses on actin regulation during myoblast fusion.

scholarly journals Fusogenic micropeptide Myomixer is essential for satellite cell fusion and muscle regeneration

2018 ◽  
Vol 115 (15) ◽  
pp. 3864-3869 ◽  
Author(s):  
Pengpeng Bi ◽  
John R. McAnally ◽  
John M. Shelton ◽  
Efrain Sánchez-Ortiz ◽  
Rhonda Bassel-Duby ◽  
...  
Keyword(s):  
Satellite Cell ◽  
Cell Fusion ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Transmembrane Protein ◽  
Myoblast Fusion ◽  
Conditional Knockout ◽  
Genetic Deletion ◽  
Specific Membrane

Regeneration of skeletal muscle in response to injury occurs through fusion of a population of stem cells, known as satellite cells, with injured myofibers. Myomixer, a muscle-specific membrane micropeptide, cooperates with the transmembrane protein Myomaker to regulate embryonic myoblast fusion and muscle formation. To investigate the role of Myomixer in muscle regeneration, we used CRISPR/Cas9-mediated genome editing to generate conditional knockout Myomixer alleles in mice. We show that genetic deletion of Myomixer in satellite cells using a tamoxifen-regulated Cre recombinase transgene under control of the Pax7 promoter abolishes satellite cell fusion and prevents muscle regeneration, resulting in severe muscle degeneration after injury. Satellite cells devoid of Myomixer maintain expression of Myomaker, demonstrating that Myomaker alone is insufficient to drive myoblast fusion. These findings, together with prior studies demonstrating the essentiality of Myomaker for muscle regeneration, highlight the obligatory partnership of Myomixer and Myomaker for myofiber formation throughout embryogenesis and adulthood.

scholarly journals Requirement of the fusogenic micropeptide myomixer for muscle formation in zebrafish

2017 ◽  
Vol 114 (45) ◽  
pp. 11950-11955 ◽  
Author(s):  
Jun Shi ◽  
Pengpeng Bi ◽  
Jimin Pei ◽  
Hui Li ◽  
Nick V. Grishin ◽  
...  
Keyword(s):  
Species Conservation ◽  
Myoblast Fusion ◽  
Amino Acid Residues ◽  
Functional Conservation ◽  
Muscle Formation ◽  
Genetic Deletion ◽  
And Function ◽  
Zebrafish Embryogenesis ◽  
Specific Membrane

Skeletal muscle formation requires fusion of mononucleated myoblasts to form multinucleated myofibers. The muscle-specific membrane proteins myomaker and myomixer cooperate to drive mammalian myoblast fusion. Whereas myomaker is highly conserved across diverse vertebrate species, myomixer is a micropeptide that shows relatively weak cross-species conservation. To explore the functional conservation of myomixer, we investigated the expression and function of the zebrafish myomixer ortholog. Here we show that myomixer expression during zebrafish embryogenesis coincides with myoblast fusion, and genetic deletion of myomixer using CRISPR/Cas9 mutagenesis abolishes myoblast fusion in vivo. We also identify myomixer orthologs in other species of fish and reptiles, which can cooperate with myomaker and substitute for the fusogenic activity of mammalian myomixer. Sequence comparison of these diverse myomixer orthologs reveals key amino acid residues and a minimal fusogenic peptide motif that is necessary for promoting cell–cell fusion with myomaker. Our findings highlight the evolutionary conservation of the myomaker–myomixer partnership and provide insights into the molecular basis of myoblast fusion.

scholarly journals The microprotein Minion controls cell fusion and muscle formation

2017 ◽  
Author(s):  
Qiao Zhang ◽  
Ajay Vashisht ◽  
Jason O’Rourke ◽  
Stéphane Y. Corbel ◽  
Rita Moran ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Fusion ◽  
Noncoding Rna ◽  
Muscle Development ◽  
Transmembrane Protein ◽  
Loss Of Function ◽  
Reading Frame ◽  
Muscle Formation ◽  
Small Open Reading Frame ◽  
Cellular Fusion

Although recent evidence has pointed to the existence of small open reading frame (smORF)-encoded microproteins in mammals, the functional repertoire of this microproteome remains to be determined1. In skeletal muscle, proper development requires fusion of mononuclear progenitors to form multinucleated myotubes, a critical but poorly understood process2,3. Here we report the identification of a small ORF encoding an essential skeletal muscle specific microprotein we term Minion (microprotein inducer of fusion). Myogenic progenitors lacking Minion differentiate normally but fail to form syncytial myotubes, and Minion-deficient mice die perinatally with marked reduction in fused muscle fibers. This fusogenic activity is conserved to the human Minion ortholog, previously annotated as a long noncoding RNA. Loss-of-function studies demonstrate that Minion is the factor providing muscle specific fusogenic function for the transmembrane protein Myomaker4. Remarkably, we demonstrate that co-expression of Minion and Myomaker is sufficient to induce rapid cytoskeletal rearrangement and homogeneous cellular fusion, even in non-muscle cells. These findings establish Minion as a novel microprotein required for muscle development, and define a two-component program for the induction of mammalian cell fusion, enabling both research and translational applications. Importantly, these data also significantly expand the known functions of smORF-encoded microproteins, an under-explored source of proteomic diversity.

scholarly journals Weak Electromagnetic Fields Accelerate Fusion of Myoblasts

2021 ◽  
Vol 22 (9) ◽  
pp. 4407
Author(s):  
Dana Adler ◽  
Zehavit Shapira ◽  
Shimon Weiss ◽  
Asher Shainberg ◽  
Abram Katz
Keyword(s):  
Skeletal Muscle ◽  
Cell Membrane ◽  
Cell Fusion ◽  
Electromagnetic Fields ◽  
Muscle Development ◽  
K Channel ◽  
Gambogic Acid ◽  
Cell Replication ◽  
Myotube Formation ◽  
Primary Myoblast

Weak electromagnetic fields (WEF) alter Ca2+ handling in skeletal muscle myotubes. Owing to the involvement of Ca2+ in muscle development, we investigated whether WEF affects fusion of myoblasts in culture. Rat primary myoblast cultures were exposed to WEF (1.75 µT, 16 Hz) for up to six days. Under control conditions, cell fusion and creatine kinase (CK) activity increased in parallel and peaked at 4–6 days. WEF enhanced the extent of fusion after one and two days (by ~40%) vs. control, but not thereafter. Exposure to WEF also enhanced CK activity after two days (almost four-fold), but not afterwards. Incorporation of 3H-thymidine into DNA was enhanced by one-day exposure to WEF (~40%), indicating increased cell replication. Using the potentiometric fluorescent dye di-8-ANEPPS, we found that exposure of cells to 150 mM KCl resulted in depolarization of the cell membrane. However, prior exposure of cells to WEF for one day followed by addition of KCl resulted in hyperpolarization of the cell membrane. Acute exposure of cells to WEF also resulted in hyperpolarization of the cell membrane. Twenty-four hour incubation of myoblasts with gambogic acid, an inhibitor of the inward rectifying K+ channel 2.1 (Kir2.1), did not affect cell fusion, WEF-mediated acceleration of fusion or hyperpolarization. These data demonstrate that WEF accelerates fusion of myoblasts, resulting in myotube formation. The WEF effect is associated with hyperpolarization but WEF does not appear to mediate its effects on fusion by activating Kir2.1 channels.

Enzyme studies of skeletal muscle in mice with hereditary muscular dystrophy

1963 ◽  
Vol 205 (5) ◽  
pp. 897-901 ◽  
Author(s):  
Marilyn W. McCaman
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Glutathione Reductase ◽  
Enzyme Activities ◽  
Lactic Dehydrogenase ◽  
Normal Muscle ◽  
Dystrophic Muscle ◽  
Nerve Section ◽  
Mouse Muscle ◽  
Dystrophic Mouse

The activities of 20 enzymes in normal, heterozygous, and dystrophic mouse muscle were studied by means of quantitative microchemical methods. Enzyme activities in normal and heterozygous muscle were essentially the same. In dystrophic muscle glucose-6-P dehydrogenase, 6-P-gluconic dehydrogenase, glutathione reductase, peptidase, ß-glucuronidase, and glucokinase activities were significantly higher than in normal muscle, while α-glycero-P dehydrogenase and lactic dehydrogenase activities were significantly lower. The pattern of enzyme activities found in normal gastrocnemius denervated by nerve section was strikingly similar to that in dystrophic muscle.

scholarly journals Smooth muscle myosin light chain kinase expression in cardiac and skeletal muscle

2000 ◽  
Vol 279 (5) ◽  
pp. C1656-C1664 ◽  
Author(s):  
B. Paul Herring ◽  
Shelley Dixon ◽  
Patricia J. Gallagher
Keyword(s):  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Cardiac Myocyte ◽  
Cardiac Tissue ◽  
Specific Protein ◽  
Myoblast Differentiation ◽  
Adult Skeletal Muscle

The purpose of this study was to characterize myosin light chain kinase (MLCK) expression in cardiac and skeletal muscle. The only classic MLCK detected in cardiac tissue, purified cardiac myocytes, and in a cardiac myocyte cell line (AT1) was identical to the 130-kDa smooth muscle MLCK (smMLCK). A complex pattern of MLCK expression was observed during differentiation of skeletal muscle in which the 220-kDa-long or “nonmuscle” form of MLCK is expressed in undifferentiated myoblasts. Subsequently, during myoblast differentiation, expression of the 220-kDa MLCK declines and expression of this form is replaced by the 130-kDa smMLCK and a skeletal muscle-specific isoform, skMLCK in adult skeletal muscle. These results demonstrate that the skMLCK is the only tissue-specific MLCK, being expressed in adult skeletal muscle but not in cardiac, smooth, or nonmuscle tissues. In contrast, the 130-kDa smMLCK is ubiquitous in all adult tissues, including skeletal and cardiac muscle, demonstrating that, although the 130-kDa smMLCK is expressed at highest levels in smooth muscle tissues, it is not a smooth muscle-specific protein.

scholarly journals Normal muscle regeneration requires tight control of muscle cell fusion by tetraspanins CD9 and CD81

2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Stéphanie Charrin ◽  
Mathilde Latil ◽  
Sabrina Soave ◽  
Anna Polesskaya ◽  
Fabrice Chrétien ◽  
...  
Keyword(s):  
Cell Fusion ◽  
Muscle Cell ◽  
Muscle Regeneration ◽  
Tight Control ◽  
Normal Muscle

Neuronotrophic effects of skeletal muscle fractions on spinal cord differentiation

Development ◽  
1982 ◽  
Vol 71 (1) ◽  
pp. 83-95
Author(s):  
L. Hsu ◽  
D. Natyzak ◽  
G. L. Trupin
Keyword(s):  
Skeletal Muscle ◽  
Spinal Cord ◽  
Neuronal Migration ◽  
Prolonged Treatment ◽  
Embryonic Chick ◽  
Neuronal Responses ◽  
Normal Muscle ◽  
Glial Development ◽  
Independent Effects ◽  
Chick Spinal Cord

Soluble fractions of homogenized skeletal muscle were found to promote neuronal migration and neuritic and glial outgrowth from embryonic chick spinal cord explants. Fractions obtained from skeletal muscle immobilized by prolonged treatment with curare were significantly more effective than normal muscle in accelerating neuronal and glial development. Fractions from other tissues such as brain and lung did not enhance neuronal differentiation, but were effective in stimulating outgrowth of glial cells. Separate measurements of glial and neuronal responses indicate that tissue fractions produce independent effects on the glial and neuronal components.

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