The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10702-7. doi: 10.1073/pnas.1004956107. Epub 2010 May 24.
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.
新出现的证据表明，神经递质乙酰胆碱（ACh）负调控神经肌肉接头的发育，但尚不清楚 ACh 是否仅通过肌肉 ACh 受体（AChR）发挥作用。在这里，我们使用遗传方法选择性地从肌肉中去除 AChR。类似于阻断 ACh 生物合成的作用，消除突触后 AChR 增加运动轴突分支并扩大神经支配区域，表明 ACh 通过突触后 AChR 负调控突触生长。然而，与阻断 ACh 生物合成的作用相反，在缺乏 agrin 的小鼠中消除突触后 AChR 未能恢复前突触和后突触分化的缺陷，表明 ACh 通过非突触后受体负调控突触分化。与这一观点一致，ACh 激动剂卡巴胆碱在体外抑制运动神经元的突触前特化。总之，这些数据表明 ACh 通过不同的细胞机制负调控神经肌肉接头处的轴突生长和突触前特化。
