Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms
Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms
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DOI：
10.1073/pnas.1004956107
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发表时间：
2010-06-08
影响因子：
11.1
通讯作者：
Lee, Kuo-Fen
中科院分区：
文献类型：
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作者：
An, Mahru C.;Lin, Weichun;Lee, Kuo-Fen
新出现的证据表明，神经递质乙酰胆碱（ACh）负性调节神经肌肉接点的发育，但尚不清楚ACh是否仅通过肌肉ACh受体（AChRs）发挥其作用。在这里，我们使用遗传方法选择性地从肌肉中去除achr。与阻断ACh生物合成的作用类似，消除突触后achr可增加运动轴突分支，扩大神经支配范围，提示ACh通过突触后achr负性调节突触生长。然而，与阻断ACh生物合成的效果相反，在agrin缺陷小鼠中消除突触后achr并不能恢复突触前和突触后分化的缺陷，这表明ACh通过非突触后受体负性调节突触分化。与这一观点一致的是，乙酰胆碱激动剂碳乙醇在体外抑制运动神经元的突触前特化。综上所述，这些数据表明ACh通过不同的细胞机制负性调节神经肌肉连接处的轴突生长和突触前特化。
Emerging evidence suggests that the neurotransmitter acetylcholine (ACh) negatively regulates the development of the neuromuscular junction, but it is not clear if ACh exerts its effects exclusively through muscle ACh receptors (AChRs). Here, we used genetic methods to remove AChRs selectively from muscle. Similar to the effects of blocking ACh biosynthesis, eliminating postsynaptic AChRs increased motor axon branching and expanded innervation territory, suggesting that ACh negatively regulates synaptic growth through postsynaptic AChRs. However, in contrast to the effects of blocking ACh biosynthesis, eliminating postsynaptic AChRs in agrin-deficient mice failed to restore deficits in pre-and postsynaptic differentiation, suggesting that ACh negatively regulates synaptic differentiation through nonpostsynaptic receptors. Consistent with this idea, the ACh agonist carbachol inhibited presynaptic specialization of motorneurons in vitro. Together, these data suggest that ACh negatively regulates axon growth and presynaptic specialization at the neuromuscular junction through distinct cellular mechanisms.