Involvement of cyclic GMP in the fusion of chick embryonic myoblasts in culture

Choi, Suk Woo; Baek, Mi Yeong; Kang, Mingyeong

doi:10.1016/0014-4827(92)90470-s

Cited by 10 publications

(7 citation statements)

References 23 publications

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“…Interestingly, after receiving differentiation cues, myoblasts show an essential and rapid spike in intracellular levels of cyclic GMP (cGMP) prior to fusion (9). Moreover, cGKI belongs to the AGC (cAMP-dependent protein kinase/ protein kinase G/protein kinase C) family of protein kinases (26) and appears to contribute to the control of cytoskeleton remodeling by phosphorylating and inactivating the VASP (6,15,31).…”

Section: Resultsmentioning

confidence: 99%

“…Cyclic GMP-dependent kinase I is activated during myoblast differentiation. It has been demonstrated previously that a spike of the second messenger cGMP is observed prior to myoblast fusion (9). Using C2C12 cells as a model, we followed the timing of the expression of FoxO1a and cGKI␣ during differentiation and compared this with phosphorylation of a known cGKI target, the cytoskeletal protein VASP, by analyz- ing the status of VASP phosphorylation on serine-239, a consensus cGKI site (33).…”

Section: Resultsmentioning

confidence: 99%

“…The timing of FoxO1a-dependent expression of cGKI␣, together with the pre-fusion spike in the levels of intracellular cGMP that accompanies muscle cell differentiation (9), should trigger cGKI␣ kinase activity. In turn, cGKI␣ should then phosphorylate FoxO1a to harness its activity and control rates of myoblast fusion.…”

Section: Resultsmentioning

confidence: 99%

“…myoblasts, which closely mimics the behavior of myoblasts expressing dominant-active FoxO1a. Following its induction by FoxO1a, cGKI␣ kinase activity is likely triggered by an essential spike in intracellular cGMP levels that accompanies myoblast cell fusion (9). cGKI␣ inhibits FoxO1a function in a rather unique manner, by phosphorylating residues that directly inhibit its DNA binding activity.…”

Section: Resultsmentioning

confidence: 99%

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FoxO1a-Cyclic GMP-Dependent Kinase I Interactions Orchestrate Myoblast Fusion

Bois

Brochard

Salin-Cantegrel

et al. 2005

Molecular and Cellular Biology

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The regulatory circuits that orchestrate mammalian myoblast cell fusion during myogenesis are poorly understood. The transcriptional activity of FoxO1a directly regulates this process, yet the molecular mechanisms governing FoxO1a activity during muscle cell differentiation remain unknown. Here we show an autoregulatory loop in which FoxO1a directly activates transcription of the cyclic GMP-dependent protein kinase I (cGKI) gene and where the ensuing cGKI activity phosphorylates FoxO1a and abolishes its DNA binding activity. These findings establish the FoxO1a-to-cGKI pathway as a novel feedback loop that allows the precise tuning of myoblast fusion. Interestingly, this pathway appears to operate independently of muscle cell differentiation programs directed by myogenic transcription factors.Fusion of cell membranes is required for the proper function and morphogenesis of several mammalian cell types, including macrophages, trophoblasts, spermatozoa and oocytes, and myoblasts that form skeletal muscle. While the mechanisms regulating intracellular membrane fusion events have been studied in some detail (4, 17), very little is known regarding the mechanisms governing mammalian cell-to-cell fusion events.Complex programs orchestrate myogenesis, which involve coordinated myogenic cell migration, recognition, adhesion, alignment, and finally membrane fusion. The FoxO family of transcription factors (FoxO1a, FoxO3, and FoxO4a) regulates diverse cellular responses, including apoptosis, cell cycle arrest, differentiation, DNA repair, and oxidative stress (1,3,7,34). While the ability of FoxO's to regulate divergent processes such as apoptosis and differentiation seems somewhat paradoxical, some of the cellular alterations associated with skeletal muscle cell differentiation do share a high degree of similarity with many phenotypic changes usually associated with apoptosis. Indeed, cytoskeleton remodeling and actin fiber disassembly are features shared by these two processes (10,14,16,29,32), and myosin light chain kinase, a conserved regulator of muscle cell contraction, is also essential for the blebbing of cell membranes observed during apoptosis (23). Furthermore, matrix metalloproteinases are required for both apoptosis and muscle cell fusion (28, 36), and activation of caspase 3, a key effector apoptotic protease, is also required for skeletal muscle cell differentiation (11).FoxO1a is essential for normal development, as evidenced by the fact that knockout mice lacking FoxO1a die at embryonic day 9.5 (E9.5) to E10.5 due to defects in vasculogenesis, whereas targeted deletions of the close FoxO1a homologs FoxO3 and FoxO4a lead to limited, if any, developmental phenotypes (8, 18). Interestingly, endothelial cells lacking FoxO1a fail to reorganize into vessel-like structures when stimulated with vascular endothelial growth factor (12), suggesting that FoxO1a directs cytoskeleton remodeling and cell-cell interactions during the formation of the vasculature. In addition, FoxO1a is both necessary and sufficient to regu...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

FoxO1a-Cyclic GMP-Dependent Kinase I Interactions Orchestrate Myoblast Fusion

Bois

Brochard

Salin-Cantegrel

et al. 2005

Molecular and Cellular Biology

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“…4±7 The neuronal (nNOS) and endothelial (eNOS) isoforms are constitutively expressed and are activated by changes in intracellular calcium, whereas the macrophage isoform is inducible (iNOS) and is independent of calcium. 8 All isoforms of NOS utilize the amino acid arginine, molecular oxygen, and NPDPH as substrates and require tetrahydrobiopterin, FAD, and FMN as cofactors. 9 NO was originally described as a mediator of smooth muscle relaxation.…”

Section: ±3mentioning

confidence: 99%

Molecular cloning and expression of nitric oxide synthase gene in chick embryonic muscle cells

Kim

Hong

Lee

et al. 1999

Cell Biochem. Funct.

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The chick skeletal muscle nitric oxide synthase (NOS) gene was cloned in order to further define the involvement of NOS in the differentiation of skeletal muscle cells. The respective cDNA had an open reading frame of 1136 amino acid residues, predicting a protein of 129,709.85 Da, and recognition sites for FAD, FMN, NADPH, and a calmodulin-binding site like those of other mammalian NOS's. Alignment of the deduced amino acid sequence revealed high homology with mammalian inducible NOS (iNOS), but not other NOS isoforms, suggesting chick skeletal muscle NOS may be an iNOS isoform. Immunoblots showed that NOS expression was highly restricted in embryonic muscle, but not in adult skeletal muscle: NOS expression markedly increased from embryonic day 9, reached a maximum by embryonic day 13, and then gradually declined until it was no longer detectable on embryonic day 19. When muscle cells obtained on embryonic day 12 were cultured, NOS expression increased transiently prior to the onset of differentiation and decreased thereafter. Inhibition of NOS expression by PDTC completely prevented muscle cell differentiation, as indicated by the inhibition of expression of myosin heavy chain and creatine kinase. The inhibitory effect of PDTC was completely reversed by addition of sodium nitroprusside, a compound that produces NO. These results clearly indicate that NOS is significantly involved in the differentiation of chick skeletal muscle cells.

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