Recycling of acetylcholine receptors at ectopic postsynaptic clusters induced by exogenous agrin in living rats.

Recycling of acetylcholine receptors at ectopic postsynaptic clusters induced by exogenous agrin in living rats.
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DOI:
10.1016/j.ydbio.2014.07.018
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发表时间:
2014-10-01
影响因子:
2.7
通讯作者:
Akaaboune, Mohammed
Akaaboune, Mohammed
中科院分区:
生物学3区
文献类型:
--
作者:
Brenner, Hans Rudolf;Akaaboune, Mohammed

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在神经肌肉连接发育过程中,运动轴突诱导乙酰胆碱受体(achr)聚集,增强其在肌膜中的代谢稳定性。在这里,我们询问突触组织者蛋白是否可能通过促进内化的achr的再循环来调节achr的代谢稳定性和密度,否则这些achr将被降解,进入突触位点。我们发现,在突触外膜由agrin诱导的无神经AChR簇中,内化的AChR被驱回异位突触簇,在那里它们与已有的和新的受体混合。AChR循环的程度取决于agrin刺激的强度,而不取决于突触后膜成熟的另一个标志——连接褶皱的发育。在慢性失神经肌肉中,AChR的稳定性和再循环都因肌肉不活动而显著降低,agrin将agrin诱导的AChR簇的再循环量维持在与失神经原始终板相似的水平。相比之下,在C2C12或原代肌管中,achr在agrin诱导的簇中没有再循环。因此,在体内肌肉中,而不是在培养的肌管中,神经蛋白促进achr的再循环,从而增加其代谢稳定性。
During the development of the neuromuscular junction, motor axons induce the clustering of acetylcholine receptors (AChRs) and increase their metabolic stability in the muscle membrane. Here, we asked whether the synaptic organizer agrin might regulate the metabolic stability and density of AChRs by promoting the recycling of internalized AChRs, which would otherwise be destined for degradation, into synaptic sites. We show that at nerve-free AChR clusters induced by agrin in extrasynaptic membrane, internalized AChRs are driven back into the ectopic synaptic clusters where they intermingle with pre-existing and new receptors. The extent of AChR recycling depended on the strength of the agrin stimulus, but not on the development of junctional folds, another hallmark of mature postsynaptic membranes. In chronically denervated muscles, in which both AChR stability and recycling are significantly decreased by muscle inactivity, agrin maintained the amount of recycled AChRs at agrin-induced clusters at a level similar to that at denervated original endplates. In contrast, AChRs did not recycle at agrin-induced clusters in C2C12 or primary myotubes. Thus, in muscles in vivo, but not in cultured myotubes, neural agrin promotes the recycling of AChRs and thereby increases their metabolic stability.
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