Rapsyn clusters and activates the synapse-specific receptor tyrosine kinase MuSK

Rapsyn clusters and activates the synapse-specific receptor tyrosine kinase MuSK
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DOI:
10.1016/s0896-6273(00)80118-x
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发表时间:
1996-05-01
期刊:
影响因子:
16.2
通讯作者:
Huganir, RL
Huganir, RL
中科院分区:
医学1区
文献类型:
--
作者:
Gillespie, SKH;Balasubramanian, S;Huganir, RL

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神经诱导的烟碱乙酰胆碱受体(AChR)的聚集需要rapsyn,突触外周膜蛋白,以及蛋白酪氨酸激酶活性。在这里,我们发现rapsyn诱导的突触特异性受体酪氨酸激酶MuSK在转染QT-6成纤维细胞的集群。此外,rapsyn刺激MUSK的自磷酸化,导致随后的细胞酪氨酸磷酸化的MuSK依赖性增加。此外,rapsyn-activated MuSK特异性磷酸化AChR β亚基,在神经支配或聚集蛋白处理肌肉期间酪氨酸磷酸化的相同亚基。这些结果表明rapsyn可能介导肌肉中MUSK的突触定位,并且MuSK可能在聚集蛋白诱导的ACI IR聚集中起重要作用。
Nerve-induced clustering of the nicotinic acetylcholine receptor (AChR) requires rapsyn, a synaptic peripheral membrane protein, as well as protein-tyrosine kinase activity. Here, we show that rapsyn induces the clustering of the synapse-specific receptor-tyrosine kinase MuSK in transfected QT-6 fibroblasts. Furthermore, rapsyn stimulates the autophosphorylation of MUSK, leading to a subsequent MuSK-dependent increase in cellular tyrosine phosphorylation. Moreover, rapsyn-activated MuSK specifically phosphorylated the AChR beta subunit, the same subunit that is tyrosine phosphorylated during innervation or agrin treatment of muscle. These results suggest rapsyn may mediate the synaptic localization of MUSK in muscle and that MuSK may play an important role in the agrin-induced clustering of the ACI IR.