Gillespie S K, Balasubramanian S, Fung E T, Huganir R L
Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Neuron. 1996 May;16(5):953-62. doi: 10.1016/s0896-6273(00)80118-x.
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 AChR.
神经诱导的烟碱型乙酰胆碱受体（AChR）聚集需要rapsyn（一种突触外周膜蛋白）以及蛋白酪氨酸激酶活性。在此，我们表明rapsyn在转染的QT-6成纤维细胞中诱导突触特异性受体酪氨酸激酶MuSK的聚集。此外，rapsyn刺激MuSK的自磷酸化，导致随后细胞酪氨酸磷酸化的MuSK依赖性增加。而且，rapsyn激活的MuSK特异性磷酸化AChRβ亚基，该亚基在肌肉的神经支配或聚集蛋白处理过程中发生酪氨酸磷酸化。这些结果表明rapsyn可能介导MuSK在肌肉中的突触定位，并且MuSK可能在聚集蛋白诱导的AChR聚集中起重要作用。
