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myoblast fusion

Maik Drechsler, Heiko Meyer, Ariane C Wilmes, Achim Paululat
Somatic muscles are formed by the iterative fusion of myoblasts into muscle fibres. This process is driven by the recurrent recruitment of proteins to the cell membrane to induce F-actin nucleation at the fusion site. Although various proteins involved in myoblast fusion have been identified, knowledge about their sub-cellular regulation is rather elusive. We identified the anaphase-promoting complex (APC/C) adaptor Fizzy related (Fzr) as an essential regulator of heart and muscle development. We show that APC/CFzr regulates the fusion of myoblasts as well as mitotic exit of pericardial cells, cardioblasts and myoblasts...
June 13, 2018: Journal of Cell Science
Rui Duan, Ji Hoon Kim, Khurts Shilagardi, Eric S Schiffhauer, Donghoon M Lee, Sungmin Son, Shuo Li, Claire Thomas, Tianzhi Luo, Daniel A Fletcher, Douglas N Robinson, Elizabeth H Chen
Spectrin is a membrane skeletal protein best known for its structural role in maintaining cell shape and protecting cells from mechanical damage. Here, we report that α/βH -spectrin (βH is also called karst) dynamically accumulates and dissolves at the fusogenic synapse between fusing Drosophila muscle cells, where an attacking fusion partner invades its receiving partner with actin-propelled protrusions to promote cell fusion. Using genetics, cell biology, biophysics and mathematical modelling, we demonstrate that spectrin exhibits a mechanosensitive accumulation in response to shear deformation, which is highly elevated at the fusogenic synapse...
June 2018: Nature Cell Biology
Masaki Tsuchiya, Yuji Hara, Masaki Okuda, Karin Itoh, Ryotaro Nishioka, Akifumi Shiomi, Kohjiro Nagao, Masayuki Mori, Yasuo Mori, Junichi Ikenouchi, Ryo Suzuki, Motomu Tanaka, Tomohiko Ohwada, Junken Aoki, Motoi Kanagawa, Tatsushi Toda, Yosuke Nagata, Ryoichi Matsuda, Yasunori Takayama, Makoto Tominaga, Masato Umeda
Myotube formation by fusion of myoblasts and subsequent elongation of the syncytia is essential for skeletal muscle formation. However, molecules that regulate myotube formation remain elusive. Here we identify PIEZO1, a mechanosensitive Ca2+ channel, as a key regulator of myotube formation. During myotube formation, phosphatidylserine, a phospholipid that resides in the inner leaflet of the plasma membrane, is transiently exposed to cell surface and promotes myoblast fusion. We show that cell surface phosphatidylserine inhibits PIEZO1 and that the inward translocation of phosphatidylserine, which is driven by the phospholipid flippase complex of ATP11A and CDC50A, is required for PIEZO1 activation...
May 24, 2018: Nature Communications
Heidi Q Xie, Yingjie Xia, Tuan Xu, Yangsheng Chen, Hualing Fu, Yunping Li, Yali Luo, Li Xu, Karl W K Tsim, Bin Zhao
Dioxin-induced toxicities that affect the development of the motor system have been proposed since many years. However, cellular evidence and the molecular basis for the effects are limited. In this study, a cultured mouse myoblast cell line, C2C12, was utilized to examine the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on myogenic differentiation and expression of acetylcholinesterase (AChE), a neuromuscular transmission-related gene. The results showed that TCDD exposure at 10-10  M repressed the myotube formation of C2C12 cells by disturbing the fusion process and suppressing the expression of myosin heavy chain, a myobute structural protein, and not by induction of cytotoxicity...
April 2018: Environmental Pollution
A Ronca, F Maiullari, M Milan, V Pace, A Gloria, R Rizzi, R De Santis, L Ambrosio
The limited number of resins, available for stereolithography applications, is one of the key drivers in research applied to rapid prototyping. In this work an acrylic photocrosslinkable resin based on methyl methacrylate (MMA), butyl methacrylate (BMA) and poly(ethylene glycol) dimethacrylate (PEGDA) was developed with different composition and characterized in terms of mechanical, thermal and biological behaviour. Two different systems have been developed using different amount of reagent. The influence of every components have been evaluated on the final characteristic of the resin in order to optimize the final composition for applications in bone tissue engineering...
September 2017: Bioactive Materials
Lianjie Hou, Jian Xu, Yiren Jiao, Huaqin Li, Zhicheng Pan, Junli Duan, Ting Gu, Chingyuan Hu, Chong Wang
BACKGROUND/AIMS: Skeletal muscle plays an essential role in the body movement. However, injuries to the skeletal muscle are common. Lifelong maintenance of skeletal muscle function largely depends on preserving the regenerative capacity of muscle. Muscle satellite cells proliferation, differentiation, and myoblast fusion play an important role in muscle regeneration after injury. Therefore, understanding of the mechanisms associated with muscle development during muscle regeneration is essential for devising the alternative treatments for muscle injury in the future...
May 3, 2018: Cellular Physiology and Biochemistry
José María Gutiérrez, Teresa Escalante, Rosario Hernández, Stefano Gastaldello, Patricia Saravia-Otten, Alexandra Rucavado
Skeletal muscle regeneration after myonecrosis involves the activation, proliferation and fusion of myogenic cells, and a coordinated inflammatory response encompassing phagocytosis of necrotic cell debris, and the concerted synthesis of cytokines and growth factors. Myonecrosis often occurs in snakebite envenomings. In the case of venoms that cause myotoxicity without affecting the vasculature, such as those of many elapid snakes, regeneration proceeds successfully. In contrast, in envenomings by most viperid snakes, which affect the vasculature and extracellular matrix in addition to muscle fibers, regeneration is largely impaired and, therefore, the muscle mass is reduced and replaced by fibro-adipose tissue...
May 1, 2018: Toxins
L Picchio, V Legagneux, S Deschamps, Y Renaud, S Chauveau, L Paillard, K Jagla
Steinert disease or Myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by toxic non-coding CUG repeat transcripts leading to altered levels of two RNA binding factors, MBNL1 and CELF1. The contribution of CELF1 to DM1 phenotypes is controversial. Here, we show that Drosophila CELF1 family member Bru - 3, contributes to pathogenic muscle defects observed in Drosophila model of DM1. Bru-3 displays predominantly cytoplasmic expression in muscles and its muscle-specific overexpression causes a range of phenotypes also observed in fly DM1 model including affected motility, fiber splitting, reduced myofiber length and altered myoblast fusion...
April 30, 2018: Disease Models & Mechanisms
Hidetoshi Sugihara, Naomi Teramoto, Keitaro Yamanouchi, Takashi Matsuwaki, Masugi Nishihara
Sarcopenia is the age-related loss of skeletal muscle mass and function. Skeletal muscle comprises diverse progenitor cells, including mesenchymal progenitor cells (MPCs), which normally support myogenic cell function but cause a decline in skeletal muscle function after differentiating into fibrous/adipose tissue. Cellular senescence is a form of persistent cell cycle arrest caused by cellular stress, including oxidative stress, and is accompanied by the acquisition of senescence-associated secretory phenotype (SASP)...
April 25, 2018: Aging
Andrea A Domenighetti, Margie A Mathewson, Rajeswari Pichika, Lydia A Sibley, Leyna Zhao, Henry G Chambers, Richard L Lieber
Cerebral palsy (CP) is the most common cause of pediatric neurodevelopmental and physical disability in the United States. It is defined as a group of motor disorders caused by a non-progressive perinatal insult to the brain. While the brain lesion is non-progressive, there is a progressive, lifelong impact on skeletal muscles, which are shorter, spastic, and may develop debilitating contractures. Satellite cells are resident muscle stem cells that are indispensable for postnatal growth and regeneration of skeletal muscles...
April 25, 2018: American Journal of Physiology. Cell Physiology
Ana Paula Irazoqui, Pablo De Genaro, Claudia Buitrago, Heinrich Bachmann, Verónica González-Pardo, Ana Russo de Boland
We have previously shown that Solanum glaucophyllum leaf extract (SGE) increases VDR protein levels and promotes myoblast differentiation. Here, we investigated whether p38 MAPK and AKT are involved in SGE actions. Cell-cycle studies showed that SGE prompted a peak of S-phase followed by an arrest in the G0/G1-phase through p38 MAPK. Time course studies showed that p38 MAPK and AKT phosphorylation were statistically increased by SGE (10 nM) or synthetic 1α,25(OH)2 D3 (1 nM) treatment. Furthermore, p38 MAPK and AKT inhibitors, SB203580 and LY294002 respectively, suppressed myoblasts fusion induced by SGE or synthetic 1α,25(OH)2 D3 We have also studied differentiation genes by qRT-PCR...
May 14, 2018: Biology Open
Olouyomi Gnimassou, Rodrigo Fernández-Verdejo, Matthew Brook, Damien Naslain, Estelle Balan, Mariwan Sayda, Jessica Cegielski, Henri Nielens, Anabelle Decottignies, Jean-Baptiste Demoulin, Kenneth Smith, Philip J Atherton, Marc Francaux, Louise Deldicque
We hypothesized that a single session of resistance exercise performed in moderate hypoxic (FiO2 : 14%) environmental conditions would potentiate the anabolic response during the recovery period spent in normoxia. Twenty subjects performed a 1-leg knee extension session in normoxic or hypoxic conditions. Muscle biopsies were taken 15 min and 4 h after exercise in the vastus lateralis of the exercised and the nonexercised legs. Blood and saliva samples were taken at regular intervals before, during, and after the exercise session...
April 19, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Jaclyn M Camuglia, Torrey R Mandigo, Richard Moschella, Jenna Mark, Christine H Hudson, Derek Sheen, Eric S Folker
BACKGROUND: A strength of Drosophila as a model system is its utility as a tool to screen for novel regulators of various functional and developmental processes. However, the utility of Drosophila as a screening tool is dependent on the speed and simplicity of the assay used. METHODS: Here, we use larval locomotion as an assay to identify novel regulators of skeletal muscle function. We combined this assay with muscle-specific depletion of 82 genes to identify genes that impact muscle function by their expression in muscle cells...
April 6, 2018: Skeletal Muscle
Ronald W Matheny, Alyssa V Geddis, Mary N Abdalla, Luis A Leandry, Michael Ford, Holly L McClung, Stefan M Pasiakos
Skeletal muscle physiology and metabolism are regulated by complex networks of intracellular signaling pathways. Among many of these pathways, the protein kinase AKT plays a prominent role. While three AKT isoforms have been identified (AKT1, AKT2, and AKT3), surprisingly little is known regarding isoform-specific expression of AKT in human skeletal muscle. To address this, we examined the expressions of each AKT isoform in muscle biopsy samples collected from the vastus lateralis of healthy male adults at rest...
March 2018: Physiological Reports
Pengpeng Bi, John R McAnally, John M Shelton, Efrain Sánchez-Ortiz, Rhonda Bassel-Duby, Eric N Olson
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...
April 10, 2018: Proceedings of the National Academy of Sciences of the United States of America
Benjamin Kalbe, Markus Osterloh, Viola M Schulz, Janine Altmüller, Christian Becker, Sabrina Osterloh, Hanns Hatt
Olfactory receptors (ORs) regulate various cellular processes in the human body. The receptors' participation in physiological and pathophysiological processes could be demonstrated in several studies. In addition to the regulation of sperm motility, respiratory physiology, and heart contraction, ORs play a crucial role in cancer cells. In murine myoblasts, mOR23 regulates the myogenesis and branching of skeletal muscle cells. To date, the expression and physiological role of ORs in human skeletal muscle cells have not been thoroughly elucidated...
May 1, 2018: Archives of Biochemistry and Biophysics
Maria Siemionow, Joanna Cwykiel, Ahlke Heydemann, Jesus Garcia, Enza Marchese, Krzysztof Siemionow, Erzsebet Szilagyi
Duchenne Muscular Dystrophy (DMD) is a progressive and lethal disease caused by mutations of the dystrophin gene. Currently no cure exists. Stem cell therapies targeting DMD are challenged by limited engraftment and rejection despite the use of immunosuppression. There is an urgent need to introduce new stem cell-based therapies that exhibit low allogenic profiles and improved cell engraftment. In this proof-of-concept study, we develop and test a new human stem cell-based approach to increase engraftment, limit rejection, and restore dystrophin expression in the mdx/scid mouse model of DMD...
June 2018: Stem Cell Reviews
Michael D Deel, Katherine K Slemmons, Ashley R Hinson, Katia C Genadry, Breanne A Burgess, Lisa E S Crose, Nina Kuprasertkul, Kristianne M Oristian, Rex C Bentley, Corinne M Linardic
Purpose: Alveolar rhabdomyosarcoma (aRMS) is a childhood soft tissue sarcoma driven by the signature PAX3-FOXO1 (P3F) fusion gene. Five-year survival for aRMS is <50%, with no improvement in over 4 decades. Although the transcriptional coactivator TAZ is oncogenic in carcinomas, the role of TAZ in sarcomas is poorly understood. The aim of this study was to investigate the role of TAZ in P3F-aRMS tumorigenesis. Experimental Design: After determining from publicly available datasets that TAZ is upregulated in human aRMS transcriptomes, we evaluated whether TAZ is also upregulated in our myoblast-based model of P3F-initiated tumorigenesis, and performed IHC staining of 63 human aRMS samples from tissue microarrays...
March 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Chayanit Chaweewannakorn, Masahiro Tsuchiya, Masashi Koide, Hiroyasu Hatakeyama, Yukinori Tanaka, Shinichirou Yoshida, Shunji Sugawara, Yoshihiro Hagiwara, Keiichi Sasaki, Makoto Kanzaki
Skeletal muscle regeneration after injury is a complex process involving interactions between inflammatory microenvironments and satellite cells. Interleukin (IL)-1 is a key mediator of inflammatory responses and exerts pleiotropic impacts on various cell types. Thus, we aimed to investigate the role of IL-1 during skeletal muscle regeneration. We herein show that IL-1α/β-double-knockout (IL-1KO) mice exhibit delayed muscle regeneration after cardiotoxin (CTX) injection, characterized by delayed infiltrations of immune cells accompanied by suppressed local production of pro-inflammatory factors including IL-6 and delayed increase of PAX7-positive satellite cells post-injury as compared with those of wild-type (WT) mice...
March 7, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Matthew Lowe, Jacob Lage, Ellen Paatela, Dane Munson, Reilly Hostager, Ce Yuan, Nobuko Katoku-Kikyo, Mercedes Ruiz-Estevez, Yoko Asakura, James Staats, Mulan Qahar, Michaela Lohman, Atsushi Asakura, Nobuaki Kikyo
Circadian rhythms regulate cell proliferation and differentiation; however, little is known about their roles in myogenic differentiation. Our synchronized differentiation studies demonstrate that myoblast proliferation and subsequent myotube formation by cell fusion occur in circadian manners. We found that one of the core regulators of circadian rhythms, Cry2, but not Cry1, is critical for the circadian patterns of these two critical steps in myogenic differentiation. This is achieved through the specific interaction between Cry2 and Bclaf1, which stabilizes mRNAs encoding cyclin D1, a G1/S phase transition regulator, and Tmem176b, a transmembrane regulator for myogenic cell fusion...
February 20, 2018: Cell Reports
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