scholarly journals Development of ultrastructural specializations during the formation of acetylcholine receptor aggregates on cultured myotubes

1986 ◽  
Vol 6 (2) ◽  
pp. 487-497 ◽  
Author(s):  
AJ Olek ◽  
A Ling ◽  
MP Daniels
Keyword(s):  
Acetylcholine Receptor ◽  
Cultured Myotubes

RNA splicing regulates agrin-mediated acetylcholine receptor clustering activity on cultured myotubes

Neuron ◽  
1992 ◽  
Vol 8 (6) ◽  
pp. 1079-1086 ◽  
Author(s):  
Michael Ferns ◽  
Werner Hoch ◽  
James T. Campanelli ◽  
Fabio Rupp ◽  
Zach W. Hall ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Rna Splicing ◽  
Receptor Clustering ◽  
Cultured Myotubes

scholarly journals Laminin induces acetylcholine receptor aggregation on cultured myotubes and enhances the receptor aggregation activity of a neuronal factor

1983 ◽  
Vol 3 (5) ◽  
pp. 1058-1068 ◽  
Author(s):  
Z Vogel ◽  
CN Christian ◽  
M Vigny ◽  
HC Bauer ◽  
P Sonderegger ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Receptor Aggregation ◽  
Cultured Myotubes ◽  
Aggregation Activity

scholarly journals Agrin Can Mediate Acetylcholine Receptor Gene Expression in Muscle by Aggregation of Muscle-derived Neuregulins

1998 ◽  
Vol 141 (3) ◽  
pp. 715-726 ◽  
Author(s):  
Thomas Meier ◽  
Fabrizio Masciulli ◽  
Chris Moore ◽  
Fabrice Schoumacher ◽  
Urs Eppenberger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neuromuscular Junction ◽  
Acetylcholine Receptor ◽  
Gene Transcription ◽  
Radioligand Binding ◽  
Muscle Fibers ◽  
Erbb Receptors ◽  
Pcr Analysis ◽  
Subunit Gene ◽  
Cultured Myotubes

The neural isoforms of agrin can stimulate transcription of the acetylcholine receptor (AChR) ε subunit gene in electrically active muscle fibers, as does the motor neuron upon the formation of a neuromuscular junction. It is not clear, however, whether this induction involves neuregulins (NRGs), which stimulate AChR subunit gene transcription in vitro by activating ErbB receptors. In this study, we show that agrin- induced induction of AChR ε subunit gene transcription is inhibited in cultured myotubes overexpressing an inactive mutant of the ErbB2 receptor, demonstrating involvement of the NRG/ErbB pathway in agrin- induced AChR expression. Furthermore, salt extracts from the surface of cultured myotubes induce tyrosine phosphorylation of ErbB2 receptors, indicating that muscle cells express biological NRG-like activity on their surface. We further demonstrate by RT-PCR analysis that muscle NRGs have Ig-like domains required for their immobilization at heparan sulfate proteoglycans (HSPGs) of the extracellular matrix. In extrasynaptic regions of innervated muscle fibers in vivo, ectopically expressed neural agrin induces the colocalized accumulation of AChRs, muscle-derived NRGs, and HSPGs. By using overlay and radioligand-binding assays we show that the Ig domain of NRGs bind to the HSPGs agrin and perlecan. These findings show that neural agrin can induce AChR subunit gene transcription by aggregating muscle HSPGs on the muscle fiber surface that then serve as a local sink for focal binding of muscle-derived NRGs to regulate AChR gene expression at the neuromuscular junction.

scholarly journals Staurosporine inhibits agrin-induced acetylcholine receptor phosphorylation and aggregation.

1994 ◽  
Vol 125 (3) ◽  
pp. 661-668 ◽  
Author(s):  
B G Wallace
Keyword(s):  
Tyrosine Phosphorylation ◽  
Acetylcholine Receptor ◽  
Tyrosine Kinases ◽  
Neuromuscular Junctions ◽  
Beta Subunit ◽  
Dependent Manner ◽  
Tyrosine Residues ◽  
Serine Kinases ◽  
Cultured Myotubes ◽  
Dose Dependent

Agrin, a protein that mediates nerve-induced acetylcholine receptor (AChR) aggregation at developing neuromuscular junctions, has been shown to cause an increase in phosphorylation of the beta, gamma, and delta subunits of AChRs in cultured myotubes. As a step toward understanding the mechanism of agrin-induced AChR aggregation, we examined the effects of inhibitors of protein kinases on AChR aggregation and phosphorylation in chick myotubes in culture. Staurosporine, an antagonist of both protein serine and tyrosine kinases, blocked agrin-induced AChR aggregation in a dose-dependent manner; 50% inhibition occurred at approximately 2 nM. The extent of inhibition was independent of agrin concentration, suggesting an effect downstream of the interaction of agrin with its receptor. Staurosporine blocked agrin-induced phosphorylation of the AChR beta subunit, which occurs at least in part on tyrosine residues, but did not reduce phosphorylation of the gamma and delta subunits, which occurs on serine/threonine residues. Staurosporine also prevented the agrin-induced decrease in the rate at which AChRs are extracted from intact myotubes by mild detergents. H-7, an antagonist of protein serine kinases, inhibited agrin-induced phosphorylation of the gamma and delta subunits but did not block agrin-induced phosphorylation of the AChR beta subunit, AChR aggregation, or the decrease in AChR extractability. The results provide support for the hypothesis that tyrosine phosphorylation of the beta subunit plays a role in agrin-induced AChR aggregation.

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