LRTM1 promotes the differentiation of myoblast cells by negatively regulating the FGFR1 signaling pathway

Li, Hao-ke; Zhou, Yong; Ding, Jian; Xiong, Lei; Shi, Yue; He, Yan-ji; Yang, Dan; Deng, Zhong‐Liang; Nie, Mao; Gao, Yan

doi:10.1016/j.yexcr.2020.112237

Cited by 8 publications

(5 citation statements)

References 36 publications

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“…5e), it appears that the interactions constrained within the loops in proliferating cells are effectively "primed" for muscle cell differentiation by the presence of MyoD, raising the possibility that some very early signal can somehow direct MyoD to occupy sites across the genome that subsequently permit both muscle-cell-appropriate loop architecture and later rewiring in response to differentiation signals. Supporting this idea, we found that Lrtm1, a myogenesis-related gene 49 that is expressed only in differentiated muscle cells (Supplementary Fig. 5f), contains chromatin loops that have already been defined by MyoD in proliferating cells (Fig.…”

Section: Resultsmentioning

confidence: 57%

MyoD is a 3D genome structure organizer for muscle cell identity

Wang

Chen

et al. 2022

Nat Commun

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The genome exists as an organized, three-dimensional (3D) dynamic architecture, and each cell type has a unique 3D genome organization that determines its cell identity. An unresolved question is how cell type-specific 3D genome structures are established during development. Here, we analyzed 3D genome structures in muscle cells from mice lacking the muscle lineage transcription factor (TF), MyoD, versus wild-type mice. We show that MyoD functions as a “genome organizer” that specifies 3D genome architecture unique to muscle cell development, and that H3K27ac is insufficient for the establishment of MyoD-induced chromatin loops in muscle cells. Moreover, we present evidence that other cell lineage-specific TFs might also exert functional roles in orchestrating lineage-specific 3D genome organization during development.

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Section: Resultsmentioning

confidence: 57%

MyoD is a 3D genome structure organizer for muscle cell identity

Wang

Chen

et al. 2022

Nat Commun

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“…FGFR downregulation was also attributed to Hrs (recently reviewed in [77]). In Hrs-depleted cells, FGFR may activate the MEK/ERK pathway as previously described [47]. Similarly, Miller et al found that dynamic of the TGF-β signaling is dictated by receptor trafficking via the ESCRT machinery, especially via the HD-PTP factor [73].…”

Section: Discussionmentioning

confidence: 58%

“…Indeed, Hrs was previously found to regulate the trafficking and/or degradation of different classes of membrane receptors in different models [41,48,73]. Like EGFR, the Toll-like receptor 4 (TLR4), the RTK fibroblast growth factor receptor (FGFR), or the transforming growth factor beta receptor (TGF-β R) activations have all been described to inhibit the differentiation of myoblasts into myotubes [47,74,75]. Interestingly, Hrs was found to regulate the trafficking and degradation of TLR4 [76] and depletion of Hrs was responsible of the accumulation of TLR4 and its activation.…”

Section: Discussionmentioning

confidence: 99%

“…The RTK family regulates several signaling pathways that may act positively or negatively on the process of myogenic differentiation. For instance, both EGFR and FGFR are negative regulator of myogenesis that need to be downregulated during differentiation [46,47]. Importantly, Hrs has a general role in regulating the trafficking, sorting, and degradation of diverse classes of signaling receptors including RTKs thus negatively modulating their activities [22,24,41,48].…”

Section: Hrs Depletion Impairs the Degradation Of The Egfr Receptor Tyrosine Kinase Rtk In C2c12mentioning

confidence: 99%

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The ESCRT-0 subcomplex component Hrs/Hgs is a master regulator of myogenesis via modulation of signaling and degradation pathways

et al. 2021

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Background Myogenesis is a highly regulated process ending with the formation of myotubes, the precursors of skeletal muscle fibers. Differentiation of myoblasts into myotubes is controlled by myogenic regulatory factors (MRFs) that act as terminal effectors of signaling cascades involved in the temporal and spatial regulation of muscle development. Such signaling cascades converge and are controlled at the level of intracellular trafficking, but the mechanisms by which myogenesis is regulated by the endosomal machinery and trafficking is largely unexplored. The Endosomal Sorting Complex Required for Transport (ESCRT) machinery composed of four complexes ESCRT-0 to ESCRT-III regulates the biogenesis and trafficking of endosomes as well as the associated signaling and degradation pathways. Here, we investigate its role in regulating myogenesis. Results We uncovered a new function of the ESCRT-0 hepatocyte growth factor-regulated tyrosine kinase substrate Hrs/Hgs component in the regulation of myogenesis. Hrs depletion strongly impairs the differentiation of murine and human myoblasts. In the C2C12 murine myogenic cell line, inhibition of differentiation was attributed to impaired MRF in the early steps of differentiation. This alteration is associated with an upregulation of the MEK/ERK signaling pathway and a downregulation of the Akt2 signaling both leading to the inhibition of differentiation. The myogenic repressors FOXO1 as well as GSK3β were also found to be both activated when Hrs was absent. Inhibition of the MEK/ERK pathway or of GSK3β by the U0126 or azakenpaullone compounds respectively significantly restores the impaired differentiation observed in Hrs-depleted cells. In addition, functional autophagy that is required for myogenesis was also found to be strongly inhibited. Conclusions We show for the first time that Hrs/Hgs is a master regulator that modulates myogenesis at different levels through the control of trafficking, signaling, and degradation pathways.

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“…Research suggests that A-kinase anchoring protein 6 (AKAP6) [ 195 ], andrographolide [ 218 ], mouse double minute 2 homolog (Mdm2)/CCAAT/enhancer-binding protein β (C/EBPβ) [ 214 ], apolipoprotein B mRNA editing enzyme catalytic polypeptide 2 (APOBEC2) knockout [ 8 ] induces the expression of MyoD, myogenin, MyoG, and desmin. Leucine-rich repeats and transmembrane domains 1 (LRTM1) inhibit the recruitment of p52Shc to FGFR1 and inhibit the activation of ERK, further reducing the inhibition of cyclin dependent kinase 4 (CDK4) on the transcriptional activity of MyoD [ 196 ]. The increased MyoD interacts with its targets transcription elongation factor A-like 7 (Tceal7) and R3h domain containing-like (R3hdml) and promotes myoblast differentiation [ 1 ].…”

Section: Mechanisms Of Regeneration In Ctx-induced Injury Modelsmentioning

confidence: 99%

Skeletal Muscle Regeneration in Cardiotoxin-Induced Muscle Injury Models

Wang

Liu

2022

IJMS

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Skeletal muscle injuries occur frequently in daily life and exercise. Understanding the mechanisms of regeneration is critical for accelerating the repair and regeneration of muscle. Therefore, this article reviews knowledge on the mechanisms of skeletal muscle regeneration after cardiotoxin-induced injury. The process of regeneration is similar in different mouse strains and is inhibited by aging, obesity, and diabetes. Exercise, microcurrent electrical neuromuscular stimulation, and mechanical loading improve regeneration. The mechanisms of regeneration are complex and strain-dependent, and changes in functional proteins involved in the processes of necrotic fiber debris clearance, M1 to M2 macrophage conversion, SC activation, myoblast proliferation, differentiation and fusion, and fibrosis and calcification influence the final outcome of the regenerative activity.

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LRTM1 promotes the differentiation of myoblast cells by negatively regulating the FGFR1 signaling pathway

Cited by 8 publications

References 36 publications

MyoD is a 3D genome structure organizer for muscle cell identity

MyoD is a 3D genome structure organizer for muscle cell identity

The ESCRT-0 subcomplex component Hrs/Hgs is a master regulator of myogenesis via modulation of signaling and degradation pathways

Skeletal Muscle Regeneration in Cardiotoxin-Induced Muscle Injury Models

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