Genetic variants of C2 muscle cells that are defective in synthesis of the alpha-subunit of the acetylcholine receptor.

Black, Roy A.; Goldman, Dan; Hochschwender, Susan M.; Lindstrom, Jon; Hall, Zach W.

doi:10.1083/jcb.105.3.1329

Cited by 24 publications

(23 citation statements)

References 44 publications

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“…We addressed the role of AChRs by utilizing the 1R – genetic variant of C2 muscle cells, a cell line which has very little surface expression of intact AChRs (Black & Hall 1985). 1R – myotubes fail to synthesize the AChR α subunit at normal rates even though they make normal amounts of AChR α subunit mRNA (Black et al . 1987).…”

Section: Introductionmentioning

confidence: 99%

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Acetylcholine receptors are required for postsynaptic aggregation driven by the agrin signalling pathway

Grow¹,

Gordon²

2000

Eur J of Neuroscience

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To investigate the role of acetylcholine receptors (AChRs) in the aggregation of postsynaptic molecules on muscle cells, we utilized the 1R- genetic variant of C2 muscle cells which has very little expression of AChRs in its cell membrane. On C2 myotubes, AChRs cluster spontaneously, with the frequency of clustering greatly enhanced by motor neuron-derived agrin. Signal transduction events driven by agrin, including the tyrosine phosphorylation of muscle-specific kinase (MuSK) and the AChR beta subunit, have been implicated as requirements of postsynaptic scaffold assembly. We show here that some molecules of the postsynaptic scaffold spontaneously aggregate and colocalize on 1R- myotubes at very low frequency, including an as yet unidentified agrin binding molecule, beta-dystroglycan and MuSK. Agrin is unable to increase the frequency of these aggregations, but does cause tyrosine phosphorylation of MuSK. We conclude that free molecules can associate into aggregates independently of AChRs, but AChRs are required for high-frequency molecular aggregation driven by the agrin signalling pathway. MuSK tyrosine phosphorylation appears to precede a requisite event involving AChRs that aggregates postsynaptic molecules.

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Section: Introductionmentioning

confidence: 99%

“…1987). Instead, they almost completely lack cell surface AChR α subunit protein, and extracts of 1R – myotube membrane and cytoplasm have only 33% of the C2 myotube amount of AChR β subunit protein (Black et al . 1987).…”

Section: Introductionmentioning

confidence: 99%

Acetylcholine receptors are required for postsynaptic aggregation driven by the agrin signalling pathway

Grow¹,

Gordon²

2000

Eur J of Neuroscience

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“…First, the synthesis of a functional ion channel might involve control at diverse levels. Subunit assembly, glycosylation, translational control, and alternative mRNA splicing each have been implicated as potential regulatory steps in ion channel formation (23)(24)(25), in addition to control at the level ofgene transcription. Second, the inference remains open to question, that growth factors and oncogenes would neces-sarily suppress Ca2l channel formation through a block to the induction of all muscle-specific genes.…”

Section: Introductionmentioning

confidence: 99%

Dihydropyridine receptor gene expression is regulated by inhibitors of myogenesis and is relatively insensitive to denervation.

Shih

Wathen²,

Marshall³

et al. 1990

J. Clin. Invest.

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To evaluate developmental and physiological signals that may influence expression of the dihydropyridine-sensitive "slow"Ca2" channel, we analyzed dihydropyridine receptor (DHPR) mRNA abundance in mouse skeletal muscle. Using synthetic oligonucleotide probes corresponding to the rabbit skeletal muscle DHPR, a 6.5 kb DHPR transcript was identified in postnatal skeletal muscle and differentiated C2 or BC3H1 myocytes, but not cardiac muscle or brain. DHPR gene expression was reversibly suppressed by 0.4 nM transforming growth factor j%-1 or by transfection with a mutant c-H-ras allele, nominal inhibitors of myogenesis that block the appearance of slow channels and DHPR. In contrast, both BC3HI and C2 myocytes containing the activated ras vector expressed the gene encoding the nicotinic acetylcholine receptor subunit, demonstrating that not all muscle-specific genes are extinguished by ras. Denervation stimulated DHPR gene expression less than 0.6-fold, despite 8-fold upregulation of 5-subunit mRNA and reciprocal effects on the skeletal and cardiac aactin genes. Thus, DHPR gene induction is prevented by inhibitors of other muscle-specific genes, whereas, at most, relatively small changes in DHPR mRNA abundance occur during adaptation to denervation. (J. Clin. Invest. 1990. 85:781-789.) calcium channels * differentiation * MyoDI -oncogenes * skeletal muscle transforming growth factor ,8-1

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“…In one case, S27 cells were cultured with 1R-cells, a variant ofthe C2C12 line that is deficient in the synthesis of the a subunit of the AChR. When cultured alone, 1R-cells have <10% of the normal amount of AChR (13). When S27 and 1R-cells were cultured together, many AChR clusters appeared, although myotubes of either variant cultured alone had none ( Fig.…”

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confidence: 99%

“…The fluorescein signal was distinguished from that of the rho-BuTx with Leitz bandpass filters. In some experiments cultures of 1R-cells (10,13) were incubated with [3H]thymidine as described (14) before being mixed and plated with S27 cells. After staining with rho-BuTx, slides with S27-1R-hybrid cultures were coated with Ilford K5 emulsion and exposed for 12 days to reveal the position of the 3H-labeled nuclei.…”

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confidence: 99%

Cooperation between the products of different nuclei in hybrid myotubes produces localized acetylcholine receptor clusters.

Gordon¹,

Ralston²,

Hall³

1992

Proc. Natl. Acad. Sci. U.S.A.

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Cultured myotubes form clusters of acetylcholine receptors (AChRs) spontaneously and at sites of nervemuscle contact. To investigate the cellular mechanisms by which spontaneous dusters are formed, we have made hybrid myotubes between a mouse muscle cell variant, S27, that does not duster AChRs, and one that does not make AChRs. We have also made hybrid myotubes using S27 and quail muscle cells. In both cases, clusters of AChRs were found near the non-S27 nuclei; in the case of the interspecific hybrids, mouse AChRs were associated with extracellular matrix components contributed by the quail nuclei. Our results suggest that AChRs made by one nucleus can be clustered by localized extracellular matrix produced by a different nucleus and provide an example of nuclear cooperation between the products of different nuclei within multinucleated muscle fibers.A basic problem in cell biology is to understand how specialized regions of the cell surface arise. This problem is a critical one for nerve cells, which can have thousands of synapses on their surfaces, each associated with a postsynaptic specialization. Adult mammalian muscle fibers, in contrast, are long, multinucleated cells with a single postsynaptic region. This region constitutes <0

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Genetic variants of C2 muscle cells that are defective in synthesis of the alpha-subunit of the acetylcholine receptor.

Cited by 24 publications

References 44 publications

Acetylcholine receptors are required for postsynaptic aggregation driven by the agrin signalling pathway

Acetylcholine receptors are required for postsynaptic aggregation driven by the agrin signalling pathway

Dihydropyridine receptor gene expression is regulated by inhibitors of myogenesis and is relatively insensitive to denervation.

Cooperation between the products of different nuclei in hybrid myotubes produces localized acetylcholine receptor clusters.

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