α-Dystroglycan Functions in Acetylcholine Receptor Aggregation But Is Not a Coreceptor for Agrin-MuSK Signaling
α-Dystroglycan Functions in Acetylcholine Receptor Aggregation But Is Not a Coreceptor for Agrin-MuSK Signaling
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α-肌营养不良聚糖在乙酰胆碱受体聚集中发挥作用，但不是 Agrin-MuSK 信号转导的共同受体
DOI：
10.1523/jneurosci.18-16-06340.1998
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
M. Ferns
中科院分区：
文献类型：
--
作者：
Christian Jacobson;F. Montanaro;M. Lindenbaum;S. Carbonetto;M. Ferns
α-肌营养不良蛋白聚糖（α-DG）是一种聚集蛋白结合蛋白，与乙酰胆碱受体（AChR）的聚集有关，但尚不清楚它是参与聚集蛋白信号传导的辅助受体，还是参与随后的事件。为了研究其作用，我们已经产生了C2小鼠肌肉细胞系的反义衍生物，其降低了α-DG表达。与野生型细胞相比，α-DG缺陷型肌管的自发和聚集蛋白诱导的AChR簇的数量显著减少。一些研究结果表明，这种减少AChR集群可能不是因为一个缺陷，聚集蛋白信号通过MuSK受体酪氨酸激酶。与野生型细胞相比，α-DG缺陷细胞系仅表现出聚集蛋白诱导的MuSK酪氨酸磷酸化水平的短暂降低，而AChR β亚基酪氨酸磷酸化水平没有降低。此外，使用缺乏主要负责与α-DG结合的结构域的聚集蛋白片段，野生型肌管中聚集蛋白诱导的MuSK磷酸化没有减少。最后，神经聚集蛋白诱导的MuSK磷酸化不受过量肌肉聚集蛋白或抗α-DG抗体等治疗的影响，这两种抗体都阻断聚集蛋白-α-DG结合。总之，这些结果表明，α-DG不是聚集蛋白-MuSK信号传导所必需的，而是它可能在聚集途径的其他地方发挥作用，例如在下游巩固或维持AChR簇。
α-dystroglycan (α-DG) is an agrin-binding protein that has been implicated in acetylcholine receptor (AChR) clustering, but it is unclear whether it acts as a coreceptor involved in initial agrin signaling or as a component involved in later events. To investigate its role, we have generated antisense derivatives of the C2 mouse muscle cell line, which have reduced α-DG expression. When compared with wild-type cells, the α-DG-deficient myotubes have a dramatic reduction in the number of spontaneous and agrin-induced AChR clusters. Several findings suggest that this decrease in AChR clustering is likely not because of a defect in agrin signaling through the MuSK receptor tyrosine kinase. Compared with wild-type cells, the α-DG-deficient cell lines showed only a transient reduction in the level of agrin-induced MuSK tyrosine phosphorylation and no reduction in AChR β-subunit tyrosine phosphorylation. Additionally, agrin-induced phosphorylation of MuSK in wild-type myotubes was not decreased using agrin fragments that lack the domain primarily responsible for binding to α-DG. Finally, neural agrin-induced phosphorylation of MuSK was unaffected by treatments such as excess muscle agrin or anti-α-DG antibodies, both of which block agrin–α-DG binding. Together, these results suggest that α-DG is not required for agrin-MuSK signaling but rather that it may play a role elsewhere in the clustering pathway, such as in the downstream consolidation or maintenance of AChR clusters.
影响因子：
13.9
作者：
M. Bowe;Justin R. Fallon
通讯作者：
M. Bowe;Justin R. Fallon