Inhibited agrin induced achr aggregation. Medical search. Frequent questions

The aim of the studies reported here was to characterize the effects of agrin on the distribution of acetylcholine receptors (AChRs) and cholinesterase as a step toward determining agrin's mechanism of action. (rupress.org)
Upon activation by its ligand agrin, MuSK signals via the proteins called casein kinase 2 (CK2), Dok-7 and rapsyn, to induce "clustering" of acetylcholine receptors (AChR). (wikipedia.org)

Blockade of L-CaChs in muscle cultures inhibited agrin-induced AChR aggregation but not tyrosine phosphorylation of MuSK or AChR beta subunits. (nih.gov)
Indeed, we found that rapsyn associated with CD4-β loop chimeras in a phosphorylation-dependent manner, and that agrin increased the ratio of rapsyn binding to wild type AChR but not to AChR-β 3F/3F , which lacks β loop tyrosine phosphorylation sites. (jneurosci.org)
Indeed, we have shown previously that mutation of a tyrosine phosphorylation site in the long cytoplasmic loop of the β subunit impairs agrin-induced cytoskeletal anchoring and aggregation of mutant AChR in muscle cells ( Borges and Ferns, 2001 ). (jneurosci.org)

Here, we define a phosphorylation-dependent binding site on the receptor that mediates agrin-induced clustering. (jneurosci.org)
The sequence contains a conserved tyrosine (Y390) whose phosphorylation is induced by agrin and whose mutation abolished clustering of β loop chimeras and their ability to inhibit agrin-induced clustering of the endogenous AChR. (jneurosci.org)
Phosphorylation of the AChR β subunit is correlated with increased rapsyn/AChR binding, suggesting that the effect of βY390 phosphorylation on clustering is mediated by rapsyn. (jneurosci.org)
Together, these findings suggest that agrin-induced phosphorylation of the β subunit motif increases the stoichiometry of rapsyn binding to the AChR, thereby helping to stably cluster the receptor and anchor it at high density in the postsynaptic membrane. (jneurosci.org)

When agrin was added to the medium bathing chick myotubes small (less than 4 micron 2) aggregates of AChRs began to appear within 2 h and increased rapidly in number until 4 h. (rupress.org)
The accumulation of AChRs into agrin-induced aggregates occurred primarily by lateral migration of AChRs already in the myotube plasma membrane at the time agrin was added to the cultures. (rupress.org)
if agrin was removed the number of aggregates declined slowly. (rupress.org)
The formation and maintenance of agrin-induced AChR aggregates required Ca++, Co++ and Mn++ inhibited agrin-induced AChR aggregation and increased the rate of aggregate dispersal. (rupress.org)

Both CK2 and Dok-7 are required for MuSK-induced formation of the neuromuscular junction, since mice lacking Dok-7 failed to form AChR clusters or neuromuscular synapses, and since downregulation of CK2 also impedes recruitment of AChR to the primary MuSK scaffold. (wikipedia.org)

Agrin, a protein extracted from the electric organ of Torpedo californica, induces the formation of specializations on cultured chick myotubes that resemble the postsynaptic apparatus at the neuromuscular junction. (rupress.org)
The similarities between agrin's effects on cultured myotubes and events that occur during formation of neuromuscular junctions support the hypothesis that axon terminals release molecules similar to agrin that induce the differentiation of the postsynaptic apparatus. (rupress.org)
At the neuromuscular junction, the acetylcholine receptor (AChR) is specifically clustered in the postsynaptic membrane via interactions with rapsyn and other scaffolding proteins. (jneurosci.org)
The mechanism by which MuSK signaling regulates the interaction of the AChR with scaffolding proteins that localize it in the postsynaptic membrane, however, remain unknown. (jneurosci.org)

Regulation of agrin-induced acetylcholine receptor aggregation by Ca++ and phorbol ester. (rupress.org)
Agrin-induced receptor aggregation also was inhibited by phorbol 12-myristate 13-acetate, an activator of protein kinase C, and by inhibitors of energy metabolism. (rupress.org)

However, neither the site of rapsyn binding by the AChR nor the factors regulating binding to it are known. (jneurosci.org)

and at agrin-induced clusters in cultured myotubes ( Wallace, 1989 ). (jneurosci.org)

Although the agrin/MuSK signaling pathway remains largely unknown, changes in intracellular calcium levels are required for agrin-induced AChR aggregation (Megeath and Fallon [1998]: J Neurosci 18: 672-678). (nih.gov)

Using chimeric proteins in which CD4 is fused to the large intracellular loop of each of the AChR subunits we found that agrin induced clustering of only chimeras containing the β subunit loop. (jneurosci.org)
The muscle AChR is a pentamer of homologous subunits, with the stoichiometry α(2), β, δ and γ (fetal) or ε (adult) subunits. (jneurosci.org)

Here, we show that L-type calcium channels (L-CaChs) are required for full agrin-induced aggregation of AChRs and sufficient to induce agrin-independent AChR aggregation. (nih.gov)
Our results establish a novel role for L-CaChs as important sources of the intracellular calcium necessary for the aggregation of AChRs. (nih.gov)

Agrin responsiveness was significantly reduced in primary muscle cultures from the muscular dysgenesis mouse, a natural mutant, which does not express the L-CaCh. (nih.gov)

However, it remains unclear where these proteins bind on the AChR and how the interactions are regulated. (jneurosci.org)

It is activated by a nerve-derived proteoglycan called agrin, which is similarly also required for neuromuscular junction formation. (wikipedia.org)