Mechanisms regulating myoblast fusion: A multilevel interplay

Lehka, Lilya; Rędowicz, Maria Jolanta

doi:10.1016/j.semcdb.2020.02.004

Cited by 91 publications

(70 citation statements)

References 140 publications

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“…Continuous assembly/disassembly of actin provides driving force for cell movement 60 . The slow turnover rate of actin also inhibits muscle cell regeneration 61 The myoblast cells then migrate and align with each other for fusion to form a multinucleated myotubes or with the pre-existing muscle sarcomere 64 . The main player of myoblast migration are Rho GTPases which includes RhoA that modulate the actin assembly and disassembly targeting actin binding proteins like Co lin 65 .…”

Section: Discussionmentioning

confidence: 99%

Generation and Characterization of Skeletal Muscle Cell based Model for GNE Myopathy: Implications in Actin Dynamics

Devi¹,

Yadav²,

Mashangva³

et al. 2020

Preprint

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UDP-N-acetyl glucosamine-2 epimerase/ N-acetyl mannosamine kinase (GNE) catalyzes key enzymatic reactions in the biosynthesis of sialic acid. Mutation in GNE gene causes GNE-Myopathy characterized by adult onset muscle weakness and degeneration. GNE is involved in different cellular processes like adhesion, apoptosis, ER stress and autophagy. Lack of appropriate model system limits drug and treatment options for GNE Myopathy as GNE knock out was found to be embryonically lethal. In the present study, we have generated L6 rat skeletal muscle cell-based model system for GNE Myopathy where GNE gene is knocked out at exon 3 using AAV mediated SEPT homology recombination. The cell line was heterozygous for GNE gene with one wild type and one truncated allele as confirmed by sequencing. The phenotype showed reduced GNE epimerase activity with little reduction in sialic acid content. In addition, the GNE knock out cell line revealed altered cytoskeletal organization with disrupted actin filament. The signaling cascade regulating actin dynamics such as Rho A, Cofilin, FAK and Src were altered leading to reduced cell migration in GNE heterozygous cells. Our study indicates possible role of GNE in regulating actin dynamics and cell migration of skeletal muscle cell. The skeletal muscle cell based system offers great potential in understanding pathomechanism and target identification for GNE Myopathy.

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Section: Discussionmentioning

confidence: 99%

Generation and Characterization of Skeletal Muscle Cell based Model for GNE Myopathy: Implications in Actin Dynamics

Devi¹,

Yadav²,

Mashangva³

et al. 2020

Preprint

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“…The authors concluded that Cr enhanced both myotube growth and myonuclear addition in a CK-and actin polymerization-dependent manner [175]. Current available evidence also suggest that ATP produced by cytosolic CK isoforms near the ends of myotubes plays a key role in myoblast fusion during myogenesis [176,177].…”

Section: Cytosol and Cytoskeletonmentioning

confidence: 99%

Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review

et al. 2021

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Creatine (Cr) is a ubiquitous molecule that is synthesized mainly in the liver, kidneys, and pancreas. Most of the Cr pool is found in tissues with high-energy demands. Cr enters target cells through a specific symporter called Na+/Cl−-dependent Cr transporter (CRT). Once within cells, creatine kinase (CK) catalyzes the reversible transphosphorylation reaction between [Mg2+:ATP4−]2− and Cr to produce phosphocreatine (PCr) and [Mg2+:ADP3−]−. We aimed to perform a comprehensive and bioinformatics-assisted review of the most recent research findings regarding Cr metabolism. Specifically, several public databases, repositories, and bioinformatics tools were utilized for this endeavor. Topics of biological complexity ranging from structural biology to cellular dynamics were addressed herein. In this sense, we sought to address certain pre-specified questions including: (i) What happens when creatine is transported into cells? (ii) How is the CK/PCr system involved in cellular bioenergetics? (iii) How is the CK/PCr system compartmentalized throughout the cell? (iv) What is the role of creatine amongst different tissues? and (v) What is the basis of creatine transport? Under the cellular allostasis paradigm, the CK/PCr system is physiologically essential for life (cell survival, growth, proliferation, differentiation, and migration/motility) by providing an evolutionary advantage for rapid, local, and temporal support of energy- and mechanical-dependent processes. Thus, we suggest the CK/PCr system acts as a dynamic biosensor based on chemo-mechanical energy transduction, which might explain why dysregulation in Cr metabolism contributes to a wide range of diseases besides the mitigating effect that Cr supplementation may have in some of these disease states.

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“…Embryonic muscle formation or repair involves myogenic precursors that mature to myoblasts which fuse with each other to give rise to a multi-nucleated myotube. The myotube further matures to form skeletal muscle tissue [57]. Previous screenings of Stabilin-2 expressing tissues missed muscle since Stabilin-2 is only expressed during myogenic differentiation through calcineurin signaling [55].…”

Section: Physiological Functions Of Stabilin-2mentioning

confidence: 99%

Role of the Hyaluronan Receptor, Stabilin-2/HARE, in Health and Disease

Harris

Baker

2020

IJMS

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Stabilin-2/HARE is the primary clearance receptor for circulating hyaluronan (HA), a polysaccharide found in the extracellular matrix (ECM) of metazoans. HA has many biological functions including joint lubrication, ocular turgor pressure, skin elasticity and hydration, cell motility, and intercellular signaling, among many others. The regulatory system for HA content in the tissues, lymphatics, and circulatory systems is due, in part, to Stabilin-2/HARE. The activity of this receptor was discovered about 40 years ago (early 1980s), cloned in the mid-1990s, and has been characterized since then. Here, we discuss the overall domain organization of this receptor and how it correlates to ligand binding, cellular signaling, and its role in known physiological disorders such as cancer.

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Mechanisms regulating myoblast fusion: A multilevel interplay

Cited by 91 publications

References 140 publications

Generation and Characterization of Skeletal Muscle Cell based Model for GNE Myopathy: Implications in Actin Dynamics

Generation and Characterization of Skeletal Muscle Cell based Model for GNE Myopathy: Implications in Actin Dynamics

Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review

Role of the Hyaluronan Receptor, Stabilin-2/HARE, in Health and Disease

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