Agrin-induced acetylcholine receptor clustering in mammalian muscle requires tyrosine phosphorylation
Agrin-induced acetylcholine receptor clustering in mammalian muscle requires tyrosine phosphorylation
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DOI：
10.1083/jcb.132.5.937
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发表时间：
1996-03-01
影响因子：
7.8
通讯作者：
Hall, Z
中科院分区：
文献类型：
--
作者：
Ferns, M;Deiner, M;Hall, Z
Agrin 被认为是神经源性因子，可启动发育中的神经肌肉接头处的乙酰胆碱受体 (AChR) 聚集。我们研究了小鼠 C2 肌管中的信号传导途径，并报告 agrin 诱导 AChR β 亚基快速但短暂的酪氨酸磷酸化。由于β亚基酪氨酸磷酸化发生在AChR簇形成之前，因此它可能作为簇机制中的前体步骤。与此一致的是，我们观察到在几个实验条件下β亚基的酪氨酸磷酸化与聚类的存在或不存在精确相关。此外，两种阻断β亚基磷酸化的酪氨酸激酶抑制剂除草霉素和十字孢菌素也阻断了集聚蛋白诱导的聚集。令人惊讶的是，这些抑制剂还分散了预先形成的 AChR 簇，这表明其他蛋白质的酪氨酸磷酸化可能是维持受体簇所必需的。这些发现表明，在哺乳动物肌肉中，集聚蛋白诱导的 AChR 聚集是通过一种需要酪氨酸磷酸化的机制发生的，并且可能涉及 AChR 本身的酪氨酸磷酸化。
Agrin is thought to be the nerve-derived factor that initiates acetylcholine receptor (AChR) clustering at the developing neuromuscular junction. We have investigated the signaling pathway in mouse C2 myotubes and report that agrin induces a rapid but transient tyrosine phosphorylation of the AChR beta subunit. As the beta-subunit tyrosine phosphorylation occurs before the formation of AChR clusters, it may serve as a precursor step in the clustering mechanism. Consistent with this, we observed that tyrosine phosphorylation of the beta subunit correlated precisely with the presence or absence of clustering under several experimental conditions. Moreover, two tyrosine kinase inhibitors, herbimycin and staurosporine, that blocked beta-subunit phosphorylation also blocked agrin-induced clustering. Surprisingly, the inhibitors also dispersed preformed AChR clusters, suggesting that the tyrosine phosphorylation of other proteins may be required for the maintenance of receptor clusters. These findings indicate that in mammalian muscle, agrin-induced AChR clustering occurs through a mechanism that requires tyrosine phosphorylation and may involve tyrosine phosphorylation of the AChR itself.