Overexpression of MyoD-inducible lysosomal sialidase (neu1) inhibits myogenesis in C2C12 cells

Champigny, Marc J.; Perry, Robert L.; Rudnicki, Michael A.; Igdoura, Suleiman A.

doi:10.1016/j.yexcr.2005.08.023

Cited by 18 publications

(13 citation statements)

References 51 publications

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“…The above mentioned results suggesting a crucial role of NEU1 in skeletal muscle growth correlate well with the observation that the expression of NEU1 is up-regulated by the muscle regulatory factor, myogenic determination gene (MyoD) on early stages of myogenesis and that the experimental overexpression of NEU1 in myoblastic cells coincides with their heightened proliferation and inhibition of the differentiation cascade [124]. Besides, early-onset sialidosis type II patients and mice with the KO NEU1 gene present with severe progressive muscular atrophy [52,125].…”

Section: Modulation Of Immune Response and Inflammationsupporting

confidence: 83%

Where catabolism meets signalling: neuraminidase 1 as a modulator of cell receptors

Pshezhetsky

Hinek

2011

Glycoconj J

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Terminal sialic acid residues are found in abundance in glycan chains of glycoproteins and glycolipids on the surface of all live cells forming an outer layer of the cell originally known as glycocalyx. Their presence affects the molecular properties and structure of glycoconjugates, modifying their function and interactions with other molecules. Consequently, the sialylation state of glycoproteins and glycolipids has been recognized as a critical factor modulating molecular recognitions inside the cell, between the cells, between the cells and the extracellular matrix, and between the cells and certain exogenous pathogens. Sialyltransferases that attach sialic acid residues to the glycan chains in the process of their initial synthesis were thought to be mainly responsible for the creation and maintenance of a temporal and spatial diversity of sialylated moieties. However, the growing evidence also suggests that in mammalian cells, at least equally important roles belong to sialidases/neuraminidases, which are located on the cell surface and in intracellular compartments, and may either initiate the catabolism of sialoglycoconjugates or just cleave their sialic acid residues, and thereby contribute to temporal changes in their structure and functions. The current review summarizes emerging data demonstrating that neuraminidase 1 (NEU1), well known for its lysosomal catabolic function, can be also targeted to the cell surface and assume the previously unrecognized role as a structural and functional modulator of cellular receptors.

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Section: Modulation Of Immune Response and Inflammationsupporting

confidence: 83%

Where catabolism meets signalling: neuraminidase 1 as a modulator of cell receptors

Pshezhetsky

Hinek

2011

Glycoconj J

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“…In addition, the expression of myogenic factors (MyoD and myogenin) was abnormal in the Neu1 −/− regenerating muscle, which indicated that Neu1 deficiency induces changes in the expression profiles of myogenic transcription factors during muscle regeneration. A previous study in C2C12 myoblasts in vitro suggested the involvement of Neu1 in the early stages of myogenesis, possibly under the regulation of MyoD [23]. The authors also showed that in the C2C12 myoblasts the activity of Neu1 is highly and temporally regulated during myogenesis.…”

Section: Discussionmentioning

confidence: 84%

“…Although we know that myopathy and muscular degeneration are part of the pathogenesis of sialidosis in children and in the mouse model, no one has investigated how myogenesis and muscle regeneration occur in the context of NEU1 deficiency in vivo. However, in vitro studies with C2C12 myoblasts have suggested that NEU1 expression is regulated by transcription factors, like MyoD, that are involved in skeletal muscle regeneration and myogenesis [22, 23]. In addition, NEU1 expression appears to be strictly controlled during the early stages of C2C12 cell differentiation, because Neu1 overexpression during the course of differentiation suppresses myogenin and myosin heavy chain expression, thus disrupting the differentiation process [23].…”

Section: Introductionmentioning

confidence: 99%

Neuraminidase-1 mediates skeletal muscle regeneration

Neves

Rizzato

Fappi

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Neuraminidase-1 (NEU1) is the sialidase responsible for the catabolism of sialoglycoconjugates in lysosomes. Congenital NEU1 deficiency causes sialidosis, a severe lysosomal storage disease associated with a broad spectrum of clinical manifestations, which also include skeletal deformities, skeletal muscle hypotonia and weakness. Neu1−/− mice, a model of sialidosis, develop an atypical form of muscle degeneration caused by progressive expansion of the connective tissue that infiltrates the muscle bed, leading to fiber degeneration and atrophy. Here we investigated the role of Neu1 in the myogenic process that ensues during muscle regeneration after cardiotoxin-induced injury of limb muscles. A comparative analysis of cardiotoxin-treated muscles from Neu1−/− mice and Neu1+/+ mice showed increased inflammatory and proliferative responses in the absence of Neu1 during the early stages of muscle regeneration. This was accompanied by significant and sequential upregulation of Pax7, MyoD, and myogenin mRNAs. The levels of both MyoD and myogenin proteins decreased during the late stages of regeneration, which most likely reflected an increased rate of degradation of the myogenic factors in the Neu1−/− muscle. We also observed a delay in muscle cell differentiation, which was characterized by prolonged expression of embryonic myosin heavy chain, as well as reduced myofiber cross-sectional area. At the end of the regenerative process, collagen type III deposition was increased compared to wild-type muscles and internal controls, indicating the initiation of fibrosis. Overall, these results point to a role of Neu1 throughout muscle regeneration.

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“…In fact, the cytosolic sialidase gradually increases during muscle differentiation (10), and an induced down-regulation of the enzyme completely inhibits muscle differentiation, suggesting that NEU2 exerts its activity by desialylating key glycoconjugates involved in the process. On the other hand, lysosomal sialidase NEU1 shows an increase of both enzyme expression and activity only during the first stages of muscle differentiation, followed by their decrease, suggesting a possible regulatory role of NEU1 in the early stages of myogenesis (12). Moreover, the NEU1 promoter was proven to be highly up-regulated by MyoD and repressed by activated MEK 3 kinase, further supporting NEU1 strong association with the differentiation process (12).…”

mentioning

confidence: 87%

“…On the other hand, lysosomal sialidase NEU1 shows an increase of both enzyme expression and activity only during the first stages of muscle differentiation, followed by their decrease, suggesting a possible regulatory role of NEU1 in the early stages of myogenesis (12). Moreover, the NEU1 promoter was proven to be highly up-regulated by MyoD and repressed by activated MEK 3 kinase, further supporting NEU1 strong association with the differentiation process (12). Surprisingly, no data are available on a possible involvement of the plasma membrane-bound sialidase NEU3 (17,18) in muscle differentiation.…”

mentioning

confidence: 97%

NEU3 Sialidase Strictly Modulates GM3 Levels in Skeletal Myoblasts C2C12 Thus Favoring Their Differentiation and Protecting Them from Apoptosis

Anastasia

Papini

Colazzo

et al. 2008

Journal of Biological Chemistry

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Membrane-bound sialidase NEU3, often referred to as the "ganglioside sialidase," has a critical regulatory function on the sialoglycosphingolipid pattern of the cell membrane, with an anti-apoptotic function, especially in cancer cells. Although other sialidases have been shown to be involved in skeletal muscle differentiation, the role of NEU3 had yet to be disclosed. Herein we report that NEU3 plays a key role in skeletal muscle differentiation by strictly modulating the ganglioside content of adjacent cells, with special regard to GM3. Induced down-regulation of NEU3 in murine C2C12 myoblasts, even when partial, totally inhibits their capability to differentiate by increasing the GM3 level above a critical point, which causes epidermal growth factor receptor inhibition (and ultimately its down-regulation) and an higher responsiveness of myoblasts to the apoptotic stimuli.Skeletal muscle differentiation is a multistep process in which myoblasts, upon exit from the cell cycle, differentiate into myocytes and eventually fuse into multinucleated myotubes (1, 2). Muscle cell commitment to differentiation is strictly regulated by a group of transcription factors, referred to as the myogenic regulatory factors (3, 4). During differentiation, a profound remodeling of both cell plasma membrane and cytoskeleton takes place, which ultimately leads to the formation of multinucleated syncytia (myotubes) (5). These events have also been shown to be associated with modifications of the cell surface lipid composition, with a key role being played particularly by sialylated glycolipids (gangliosides) (6 -8). Along this line, sialidases (9), the enzymes that specifically remove sialic acid from sialylated glycoconjugates, have been shown to participate in the regulation of the myogenic event (10 -12). These findings further corroborate the evidence that sialidases, and their sialylated substrates, are fundamental in many physiological processes and that their de-regulation may lead to different pathologies, including cancer (13-16). Mammals possess four different sialidases (NEU1, NEU2, NEU3, NEU4) with different subcellular localization and substrate specificity, suggesting that each of them may possess a characteristic role. Actually, the cytosolic sialidase NEU2 and the lysosomal sialidase NEU1 seem to have different functions in skeletal muscle differentiation. In fact, the cytosolic sialidase gradually increases during muscle differentiation (10), and an induced down-regulation of the enzyme completely inhibits muscle differentiation, suggesting that NEU2 exerts its activity by desialylating key glycoconjugates involved in the process. On the other hand, lysosomal sialidase NEU1 shows an increase of both enzyme expression and activity only during the first stages of muscle differentiation, followed by their decrease, suggesting a possible regulatory role of NEU1 in the early stages of myogenesis (12). Moreover, the NEU1 promoter was proven to be highly up-regulated by MyoD and repressed by activated MEK 3 kinase, further ...

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Overexpression of MyoD-inducible lysosomal sialidase (neu1) inhibits myogenesis in C2C12 cells

Cited by 18 publications

References 51 publications

Where catabolism meets signalling: neuraminidase 1 as a modulator of cell receptors

Where catabolism meets signalling: neuraminidase 1 as a modulator of cell receptors

Neuraminidase-1 mediates skeletal muscle regeneration

NEU3 Sialidase Strictly Modulates GM3 Levels in Skeletal Myoblasts C2C12 Thus Favoring Their Differentiation and Protecting Them from Apoptosis

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