The role of an agrin-growth factor interaction in ACh receptor clustering
The role of an agrin-growth factor interaction in ACh receptor clustering
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DOI：
10.1006/mcne.1996.0063
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发表时间：
1996-01-01
影响因子：
3.5
通讯作者：
Peng, HB
中科院分区：
文献类型：
--
作者：
Daggett, DF;Cohen, MW;Peng, HB
乙酰胆碱受体（acetylcholine receptor，AChRs）在神经肌肉接头处的聚集部分是由硫酸乙酰肝素蛋白聚糖聚集蛋白介导的。然而，我们以前的研究也表明了肝素结合生长相关分子（heparin-binding growth-associated molecule，HB-GAM）在AChR聚集中的作用。发现聚集蛋白包被的珠粒在AChR簇诱导中效果弱，而进一步用HB-GAM处理的聚集蛋白包被的珠粒在AChR簇诱导中非常有效。蛋白质覆盖测定显示HB-GAM与聚集蛋白的特异性结合。此外，聚集蛋白富集的神经炎径迹以显示神经聚集蛋白和所应用的因子之间高度共定位的方式结合HB-GAM。外源HB-GAM与可溶性聚集蛋白一起的引入导致AChR簇以聚集蛋白同种型依赖的方式出现在细胞的背表面上;与在单独的聚集蛋白反应中观察到的特征性腹侧AChR簇相比，这是一个显著的变化。这些结果表明，聚集蛋白可能介导AChR集群与肌肉结合的肝素结合生长因子，如HB-GAM相互作用。
The clustering of acetylcholine receptors (AChRs) at the neuromuscular junction is mediated in part by the heparan-sulfate proteoglycan agrin, However, our previous studies have also suggested the role of heparin-binding growth-associated molecule (HB-GAM) in AChR clustering, Here the role of an agrin-HB-GAM interaction in this process was examined using cultured Xenopus muscle cells. Agrin-coated beads were found to be weakly effective while agrin-coated beads further treated with HB-GAM were highly effective in AChR cluster induction, Protein overlay assays showed specific binding of HB-GAM to agrin, In addition, agrin-enriched neuritic tracks bound HB-GAM in a manner that showed a high degree of colocalization between the neural agrin and the applied factor Finally, the introduction of exogenous HB-GAM together with soluble agrin resulted in the appearance of AChR clusters on the dorsal surface of cells in an agrin isoform-dependent manner; a dramatic change from the characteristic ventral AChR clustering seen in response to agrin alone. These results suggest that agrin may mediate AChR clustering by interacting with muscle-bound heparin-binding growth factors such as HB-GAM.