Identification and characterization of novel Kirrel isoform during myogenesis

Durcan, Peter Joseph; Al-Shanti, Nasser; Stewart, Claire E.

doi:10.1002/phy2.44

Cited by 7 publications

(5 citation statements)

References 55 publications

(126 reference statements)

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“…This process is remarkably conserved between flies and vertebrates [ 116 ], where the Sns/Hbs orthologue Nephrin is required for myoblast fusion [ 113 ], and this binds to the Duf/Rst vertebrate orthologues Kirrel1, Kirrel2, and Kirrel3 (a.k.a. Neph1, Neph2, Neph3) [ 27 ]. At the site of fusion, the Arf-GEF Schizo (a.k.a.…”

Section: Introductionmentioning

confidence: 99%

Amphioxus muscle transcriptomes reveal vertebrate-like myoblast fusion genes and a highly conserved role of insulin signalling in the metabolism of muscle

2022

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Background The formation and functioning of muscles are fundamental aspects of animal biology, and the evolution of ‘muscle genes’ is central to our understanding of this tissue. Feeding-fasting-refeeding experiments have been widely used to assess muscle cellular and metabolic responses to nutrition. Though these studies have focused on vertebrate models and only a few invertebrate systems, they have found similar processes are involved in muscle degradation and maintenance. Motivation for these studies stems from interest in diseases whose pathologies involve muscle atrophy, a symptom also triggered by fasting, as well as commercial interest in the muscle mass of animals kept for consumption. Experimentally modelling atrophy by manipulating nutritional state causes muscle mass to be depleted during starvation and replenished with refeeding so that the genetic mechanisms controlling muscle growth and degradation can be understood. Results Using amphioxus, the earliest branching chordate lineage, we address the gap in previous work stemming from comparisons between distantly related vertebrate and invertebrate models. Our amphioxus feeding-fasting-refeeding muscle transcriptomes reveal a highly conserved myogenic program and that the pro-orthologues of many vertebrate myoblast fusion genes were present in the ancestral chordate, despite these invertebrate chordates having unfused mononucleate myocytes. We found that genes differentially expressed between fed and fasted amphioxus were orthologous to the genes that respond to nutritional state in vertebrates. This response is driven in a large part by the highly conserved IGF/Akt/FOXO pathway, where depleted nutrient levels result in activation of FOXO, a transcription factor with many autophagy-related gene targets. Conclusion Reconstruction of these gene networks and pathways in amphioxus muscle provides a key point of comparison between the distantly related groups assessed thus far, significantly refining the reconstruction of the ancestral state for chordate myoblast fusion genes and identifying the extensive role of duplicated genes in the IGF/Akt/FOXO pathway across animals. Our study elucidates the evolutionary trajectory of muscle genes as they relate to the increased complexity of vertebrate muscles and muscle development.

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Section: Introductionmentioning

confidence: 99%

Amphioxus muscle transcriptomes reveal vertebrate-like myoblast fusion genes and a highly conserved role of insulin signalling in the metabolism of muscle

2022

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“…Nephrin, a cell surface protein, has been shown to be essential for myocyte fusion in mice and normal muscle development in zebrafish (1). The protein Kirrel, the homolog of the Drosophila Kirre protein, is also necessary for proper fusion of myocytes in zebrafish (2), although its function in mammals has not yet been confirmed and remains a subject of debate (3). In zebrafish, a receptor ligand pair (Jam-b/Jam-c) has been reported to be involved in myocyte fusion (4).…”

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confidence: 99%

Trout myomaker contains 14 minisatellites and two sequence extensions but retains fusogenic function

Landemaine

Ramirez-Martinez

Monestier

et al. 2019

Journal of Biological Chemistry

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The formation of new myofibers in vertebrates occurs by myoblast fusion and requires fusogenic activity of the musclespecific membrane protein myomaker. Here, using in silico (BLAST) genome analyses, we show that the myomaker gene from trout includes 14 minisatellites, indicating that it has an unusual structure compared with those of other animal species. We found that the trout myomaker gene encodes a 434 -amino acid (aa) protein, in accordance with its apparent molecular mass (ϳ40 kDa) observed by immunoblotting. The first half of the trout myomaker protein (1-220 aa) is similar to the 221-aa mouse myomaker protein, whereas the second half (222-234 aa) does not correspond to any known motifs and arises from two protein extensions. The first extension (ϳ70 aa) apparently appeared with the radiation of the bony fish clade Euteleostei, whereas the second extension (up to 236 aa) is restricted to the superorder Protacanthopterygii (containing salmonids and pike) and corresponds to the insertion of minisatellites having a length of 30 nucleotides. According to gene expression analyses, trout myomaker expression is consistently associated with the formation of new myofibers during embryonic development, postlarval growth, and muscle regeneration. Using cell-mixing experiments, we observed that trout myomaker has retained the ability to drive the fusion of mouse fibroblasts with C2C12 myoblasts. Our work reveals that trout myomaker has fusogenic function despite containing two protein extensions.

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“…Based on these previous results, SEZ6L2 may modulate the cell cycle and metastasis of osteosarcoma through regulation by STAT3, EGR1 and PAX4. KIRREL, also known as NEPH1, is a nephrin-associated member of the immunoglobulin superfamily that is involved in cell-cell interaction and somatic cell fusion during embryonic development (27,28). Notably, it is thought that somatic cell fusion may be a mechanism that contributes to cancer metastasis and chemotherapy resistance (29,30).…”

Section: Discussionmentioning

confidence: 99%

CpG methylation patterns are associated with gene expression variation in osteosarcoma

Wang

2017

Molecular Medicine Reports

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Osteosarcoma is a common malignant tumor in childhood and adolescence (nearly 5% of all cases of cancer in children), as well as a type of tumor with poor prognosis. However, the pathogenesis and molecular mechanisms of osteosarcoma remains to be elucidated. The aim of the current study was to determine the association between methylation and gene expression changes in osteosarcoma cell line. Microarray data were obtained from the Gene Expression Omnibus database (GSE36004). Genome‑wide methylation status was determined in 19 different osteosarcoma cell lines and 6 normal controls. Differentially expressed genes (DEGs) were identified from cancer cells with genefilter package in R and differentially methylated sites were screened with CpGassoc package in R. Integrated gene expression with methylation profiles, genes differentially expressed and methylated, were obtained, and transcriptional regulatory network construction was performed. Functional annotation was performed for genes in the network using the DAVID online tool. Following integrated analysis, a total of 75 methylated sites were demonstrated to be localized at a transcription factor binding region. These sites may be bound by 83 transcription factors which will then alter the expression of 75 downstream DEGs. In the regulatory network, seizure related 6 homolog like 2 (SEZ6L2) had the highest degree of upregulation and was demonstrated to be regulated by 12 transcription factors. Furthermore, kin of IRRE like (KIRREL), centrosomal protein 72 (CEP72) and cyclin‑dependent kinase 4 (CDK4) were also regulated by more than three transcription factors. Functional annotation revealed that the upregulated genes were primarily involved in the cell cycle pathway. Several differentially methylated sites were associated with upregulation of SEZ6L2, KIRREL, CEP72 and CDK4 and may have an important role in the pathogenesis of osteosarcomas through promotion of cell proliferation and metastasis.

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Identification and characterization of novel Kirrel isoform during myogenesis

Cited by 7 publications

References 55 publications

Amphioxus muscle transcriptomes reveal vertebrate-like myoblast fusion genes and a highly conserved role of insulin signalling in the metabolism of muscle

Amphioxus muscle transcriptomes reveal vertebrate-like myoblast fusion genes and a highly conserved role of insulin signalling in the metabolism of muscle

Trout myomaker contains 14 minisatellites and two sequence extensions but retains fusogenic function

CpG methylation patterns are associated with gene expression variation in osteosarcoma

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