Association of muscle-specific kinase MuSK with the acetylcholine receptor in mammalian muscle
Association of muscle-specific kinase MuSK with the acetylcholine receptor in mammalian muscle
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DOI：
10.1093/emboj/16.16.4951
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发表时间：
1997-08-15
期刊：
影响因子：
11.4
通讯作者：
Hall, ZW
中科院分区：
文献类型：
--
作者：
Fuhrer, C;Sugiyama, JE;Hall, ZW
在神经肌肉接头处的突触发生期间，神经释放的因子聚集蛋白引起乙酰胆碱受体（AChR）在神经末梢下方的肌膜中聚集。聚集蛋白通过特异性受体起作用，该受体被认为具有受体酪氨酸激酶MuSK作为其组分之一。在聚集蛋白处理的肌细胞中，MuSK和hChR都变得酪氨酸磷酸化。为了确定MuSK的激活如何导致AChR聚集，我们研究了它们在培养的C2肌管中的相互作用。免疫沉淀实验表明，MuSK与乙酰胆碱受体，这种关联增加了聚集蛋白治疗。在agrin处理的肌管中，MuSK磷酸化与AChR β亚基磷酸化的时间过程相同，但下降更快。尽管除莠霉素和星形孢菌素都阻断了agrin诱导的AChR磷酸化，但只有除莠霉素抑制了MuSK的磷酸化。这些结果表明，尽管聚集蛋白增加了与AChR相关的活化MuSK的量，但MuSK并不直接负责AChR磷酸化，而是通过其他激酶起作用。
During synaptogenesis at the neuromuscular junction, a neurally released factor, agrin, causes the clustering of acetylcholine receptors (AChRs) in the muscle membrane beneath the nerve terminal. Agrin acts through a specific receptor which is thought to have a receptor tyrosine kinase, MuSK, as one of its components. In agrin-treated muscle cells, both MuSK and the hChR become tyrosine phosphorylated, To determine how the activation of MuSK leads to AChR clustering, we have investigated their interaction in cultured C2 myotubes. Immunoprecipitation experiments showed that MuSK is associated with the AChR and that this association is increased by agrin treatment. Agrin also caused a transient activation of the AChR-associated MuSK, as demonstrated by MuSK phosphorylation, In agrin-treated myotubes, MuSK phosphorylation increased with the same time course as phosphorylation of the beta subunit of the AChR, but declined more quickly, Although both herbimycin and staurosporine blocked agrin-induced AChR phosphorylation, only herbimycin inhibited the phosphorylation of MuSK. These results suggest that although agrin increases the amount of activated MuSK that is associated with the AChR, MuSK is not directly responsible for AChR phosphorylation but acts through other kinases.